9. 3. Drug discovery and design. Unit 9: Medicinal Chemistry
|
|
- Caren Boone
- 7 years ago
- Views:
Transcription
1 9. 3 Drug discovery and design Modern chemical techniques have revolutionised the process of drug design. A knowledge of the structure of receptor sites and computer modelling techniques to predict the binding of drug molecules to these sites means that research is now able to identify likely candidates for new drugs before the drug has even been synthesised by chemists. nce compounds are identified, new combinatorial techniques allow chemists to synthesise large numbers of structurally related molecules to enable rapid identification of the most promising candidate for further development. In this unit you will look at how these new techniques of computer modelling and combinatorial chemistry are being applied in modern drug design and development. n successful completion of this topic you will: understand the stages of drug discovery and design (L3). To achieve a Pass in this unit you need to show that you can: discuss the issues for consideration when designing a new drug (3.1) explain the concepts of structure-activity relationships with respect to drug design (3.2) explain the role of combinatorial chemistry in drug synthesis and development (3.3). 1
2 1 Designing a new drug Dr Richard Lewis, Global Head of Computeraided Drug Design at ovartis International Dr Richard Lewis is the global head of Computer-aided Drug Design at ovartis International, a multinational pharmaceutical company based in Basel, Switzerland. He talks about the drug discovery process and gives some examples of how the various disciplines involved in the process interact with each other. You can read more about the chemical and biochemical aspects of the research in sections 2 and 3 of this topic guide. The essential principle is that we aim to invent safe drugs for unmet medical needs. With modern chemical and computing techniques we can make and investigate a myriad of new compounds. There are so many avenues we could go down, but ultimately we have to take pragmatic decisions to ensure that we can deliver a successful product in a reasonable time frame. We need to begin by identifying a disease that is amenable to drug intervention. We will need to know its biology what is the pathway by which the disease operates? Are there reactions or processes within that pathway which could be somehow disrupted? Can this disruption be enabled by the relatively small molecules, which we will be aiming to design and develop? Even at this stage we may need to be looking further ahead before we know whether we have a viable project. Assuming that these theoretical studies look promising, we would need to have some confidence that we will be able to evaluate the project at different stages how will we screen the molecules we develop to help identify the most promising target molecules? Will the effects of the drugs be measurable in clinical trials? Is it likely to be technically and financially feasible to develop this into a marketable drug? A good example of recent research, which illustrates the principles of drug design, takes Alzheimer s disease as a target. Clearly the potential market for a drug that has demonstrable efficacy in reducing symptoms or slowing the disease progression would be enormous. The target reaction is one in which an enzyme called BACE-1 cleaves a protein known as the amyloid precursor protein. Cleavage of this protein is known to be an important step along the route that eventually leads to the build-up of the plaques, which are observed in the brains of Alzheimer s patients. nce we have identified a target reaction in this way we need to identify molecules known as lead compounds which can act as ligands by bonding strongly to the binding site of the enzyme and thereby inhibit it. The starting point for this might be the natural substrate for the enzyme, but even screening analogues of this will be a potentially lengthy and costly process; the conventional method for finding a hit in this way might have been to perform high-throughput screening. In this process, maybe as many as a million different compounds are synthesised and their ability to act as a ligand tested by a suitable assay procedure. In the research projects that I manage, we use computer modelling to carry out structure-based pharmacophore screening. The detailed three-dimensional structure of the binding site is established, using X-ray crystallography allied to MR spectroscopy. Then computer modelling can be used to deduce the likely structure of the pharmacophore the part of the ligand molecule that enables it to be recognised at the binding site. Quantitative structure-activity relationship models can be used to predict the most effective ligands based on our knowledge of the pharmacophore and, as a result, we can prioritise the experimental investigation of just the most likely ligands. It is tempting to imagine that identifying an effective ligand for an enzyme such as BACE-1 might be a real breakthrough in Alzheimer s research. In reality, however, it is just one very small step along the way towards a treatment that may have some promise in the future. For the lead compounds that we identify to become a drug, other research teams must find ways of adjusting its structure to ensure that it is very specific in its inhibition of BACE-1 and that it has suitable hydrophobic and polar properties to allow it to be absorbed, distributed, metabolised and excreted at a suitable rate. If they achieve this then it is just possible that the drug may show some useful efficacy in human beings. Drug discovery involves genuine partnership across a wide range of disciplines. It is a wonderfully varied and challenging field to work in, and one in which we know that the data we obtain today may one day lead to a better and longer life for maybe millions of patients. 2
3 Figure 9.3.1: The three key stages of drug discovery and design. Target identification Choosing the disease Choosing a drug target Identifying a lead compound Identifying a screening method Finding a lead compound Isolating, purifying and identifying its structure ptimising the lead compound Ensuring specificity ptimising rate of absorption, metabolism, etc. Maximising efficacy Link You will learn more about the processes that Dr Lewis describes in the presentation Drug Design. Activity The three key stages of drug discovery and design (see Figure 9.3.1) can be described as: 1 target identification 2 identifying lead compounds by screening 3 lead optimisation. Look at Dr Lewis s description of the research into BACE-1 inhibitors. Explain what happened in each of these stages. 2 Structure-activity relationships Link There are some examples of threedimensional representations of binding sites and ligands in the presentation Drug Design. Key terms Analogues: Molecules with structural similarities to the lead compound. Screening: A procedure used to predict the biological activity of a drug or other biochemical substance. Lead compound: A molecule with proven biological activity that is the starting point for a development process to become an effective drug. Pharmacophore: The part of the structure of a drug molecule responsible for its pharmacological action. In the context of drug design it can also mean the part of the molecule which binds to a binding site. Structure-activity relationship and drug design Drug design is based on the basic premise that molecules with similar structures will display similar activities this principle is known as the structure-activity relationship. If a molecule, for example, a naturally occurring metabolite, could be shown to have some biological activity, then molecules with similar structures might show the same (or enhanced) activity. The traditional model of drug design involved screening these molecules by performing in vitro assays on a range of possible drug candidates and hence identifying one or more lead compounds that show promising levels of activity. Lead compounds are then chemically modified to increase their effectiveness in a process known as lead optimisation. This process can be made more targeted by making use of structure-activity relationships: if the three-dimensional position of functional groups in a binding site is known, then deductions can be made about where a ligand may bind. This is done using powerful computer software, and the use of these computational techniques to screen molecules is often referred to as in silico screening. Pharmacophore A key aspect of drug design is the identification of the pharmacophore. This can be done by examining the structural features of molecules that show activity in the assays, but modern computing techniques allow the pharmacophore structure to be deduced directly from the structure of the binding site. Such modelling requires a very detailed knowledge of the three-dimensional structure of the binding site. This is obtained by combining a range of techniques such as X-ray crystallography and MR spectroscopy. 3
4 Figure 9.3.2: A wide variety of possible ligands can be created by adding substituents to an identified pharmacophore (circled). Varying the substituents nce the structure of the pharmacophore is established, a range of molecules with different substituents (for example, by adding a range of groups to free hydroxyl or amine groups in the pharmacophore). S H H H H H H H H H H 2 H H H H H H H 2 H H H H Link You will find out more about how computer-aided drug design allows chemists to design drugs that bind effectively to the target receptor site in the presentation Drug Design. Key terms Lipophilicity: The tendency of a molecule to dissolve in non-polar solvents such as lipids. Partition coefficient: The ratio of the concentrations of a solute in two different solvents once equilibrium has been reached. Hydrophilicity: The tendency of a molecule to dissolve in water. Quantitative structure-activity relationships (QSAR) Attempting to quantify structure-activity relationships allows drug designers to more rapidly identify likely drug molecules. While it is true that such methods have a significant level of uncertainty attached to them, the use of quantitative data allied to the chemists knowledge of the behaviour of functional groups is providing an increasingly valuable tool. Surprisingly, QSAR modelling techniques date from well before the era of computer-aided drug design. Early methods involved characterising the groups present in a potential drug molecule by parameters such as their lipophilicity. This is measured by calculating the partition coefficient, P i, which is calculated by knowing the concentration of the compound in octan-1-ol and water at equilibrium with one another: concentration of compound in octan-1-ol P i = concentration of compound in water A high partition coefficient indicates high lipophilicity and low hydrophilicity. The overall contribution of these parameters to the likely activity of the molecule could then be estimated by mathematical manipulation. Take it further A highly detailed survey of the way in which QSAR has developed, taken from Medicinal Chemistry and Drug Discovery, (Burger, 2003) can be found at This includes information about the different models of combining parameters and tables of data for some of the main parameters that characterise the drug-receptor binding, for example, hydrophobicity P i, molar refractivity (related to the polarisability) and various steric factors. QSAR data is frequently included in research papers and you will be able to see how the data is used to produce an overall measure of biological activity. 4
5 Checklist At the end of this section, you should be familiar with the following ideas: knowledge of the structure of the binding site allows the structure of a pharmacophore to be deduced structure-activity relationships can be used to predict the effect of making changes to the pharmacophore quantitative structure-activity relationships are used to help design drug structures using numerical data. 3 Combinatorial chemistry As seen earlier, drug discovery and development requires that a large number of molecules with structural similarities can be synthesised quickly and cheaply to enable their activity to be assayed (screened). This is enabled by combinatorial methods. The techniques of combinatorial chemistry were first devised to enable polypeptide synthesis but have now been extended for use in the synthesis of a wide range of products. A very simple example of a combinatorial method would be the synthesis of a range of amides (see Figure 9.3.3). In each reaction, the reaction conditions and reaction vessels will be the same. Figure 9.3.3: A simple example of combinatorial chemistry. ine different possible products can be formed by combining these two combinatorial libraries. Amine R 1 H 2 R 2 H 2 + Acyl chloride R 4 R 5 CCl CCl Amide R 1 H C R 4 R 1 H C R 5 R 3 H 2 R 6 CCl R 1 H C R 6 R 2 H C R 4 Combinatorial libraries R 2 H C R 5 R 2 H C R 6 R 3 H C R 4 R 3 H C R 5 Combinatorial libraries Principles of synthesis R 3 H C R 6 Products In drug synthesis, the combinatorial reaction involves a starting material that is thought likely to have some biological activity. A range of molecules with a similar structure is prepared to form the first combinatorial library. There will be a core portion of the molecule common to all the members of this library, known as the scaffold structure. 5
6 The second combinatorial library used in the synthesis will then consist of a range of related reagents. The 20 starting materials and 50 reagents would then create a potential for 1000 first round products. The synthesis can then continue with a second step to modify the scaffold structure still further; if 50 further reagents are used then there will be 50,000 second round products to screen (see Figure 9.3.4). Figure 9.3.4: The number of possible products which can be produced by combinatorial techniques multiplies rapidly in multi-step syntheses. Starting materials 20 molecules Reagents 50 molecules First round products 1000 Reagents 50 molecules Second round products 50,000 molecules Activity Use research to find details of combinatorial libraries used in the search for a specific lead compound. Use the structures of the molecules in each library to identify the scaffold structure. Key term ligo-: A prefix used to denote a small number (<50) of monomer molecules bonded together to form larger molecules. Take it further A full guide to the current principles of combinatorial chemistry can be found at There are some interesting examples of combinatorial libraries readily available on the internet. A good example is at Techniques used in combinatorial chemistry Combinatorial chemistry was first used in the 1980s as a technique for producing large numbers of oligopeptides and oligonucleotides. Modern combinatorial chemistry is now a critical step in the process of high-throughput screening, which is necessary for the identification of lead compounds and lead optimisation processes. Solid support method This was the first combinatorial technique to be used. In this method the starting material is attached to beads of resin and divided into a number of portions. Each of these is then exposed to a different reagent. The product, still attached to the resin, can easily be separated from unreacted reagents and co-products and the process can be continued for as many steps as necessary to produce the required number of products. In some cases the screening of the product can take place while still attached to the resin. Solution synthesis If it is difficult to attach the starting material to a suitable resin, or if it is desired to monitor the progress of the reaction while the product is being formed, then the reactions can be carried out in solution, as in conventional synthesis. This does, however, create problems in separating and purifying a large number of different product molecules. 6
7 Parallel synthesis Both of these techniques are used in what is called parallel synthesis. A large number of product molecules are synthesised at the same time and all of them are screened concurrently. This is in contrast to more traditional methods of synthesis where a single compound is made and screened, and the results of that screening are then used to inform the decision about which molecule to synthesise next. Portfolio activity (2.3, 3.1, 3.2, 3.3) Write a description of the processes of drug discovery and design. You should illustrate your description wherever possible with some examples of how these processes have been applied to specific examples of drugs. Suitable examples could come from some of the drugs discussed in Topic guide 9.4 for example, the penicillins, ACE inhibitors such as captopril and anticancer drugs such as methotrexate. In your description you should cover the following: how drug targets are chosen and lead compounds identified how structure activity relationships are applied to the design of the drug how combinatorial chemistry is used in the in vitro or in silico screening of possible drug candidates how drugs are evaluated for biological activity and safety. Checklist At the end of this section, you should be familiar with the following ideas: large numbers of similar molecules need to be synthesised during the process of drug design combinatorial libraries are used to enable these molecules to be assembled. Acknowledgements The publisher would like to thank the following for their kind permission to reproduce their photographs: Shutterstock.com: isak55 All other images Pearson Education We are grateful to the following for permission to reproduce copyright material: Dr Richard Lewis, ovartis International AG Investor Relations for a case study. Reproduced with kind permission. In some instances we have been unable to trace the owners of copyright material, and we would appreciate any information that would enable us to do so. 7
Combinatorial Chemistry and solid phase synthesis seminar and laboratory course
Combinatorial Chemistry and solid phase synthesis seminar and laboratory course Topic 1: Principles of combinatorial chemistry 1. Introduction: Why Combinatorial Chemistry? Until recently, a common drug
More informationSTRUCTURE-GUIDED, FRAGMENT-BASED LEAD GENERATION FOR ONCOLOGY TARGETS
STRUCTURE-GUIDED, FRAGMENT-BASED LEAD GENERATION FOR ONCOLOGY TARGETS Stephen K. Burley Structural GenomiX, Inc. 10505 Roselle Street, San Diego, CA 92121 sburley@stromix.com www.stromix.com Summary Structural
More informationPharmacology skills for drug discovery. Why is pharmacology important?
skills for drug discovery Why is pharmacology important?, the science underlying the interaction between chemicals and living systems, emerged as a distinct discipline allied to medicine in the mid-19th
More informationIntegrating Medicinal Chemistry and Computational Chemistry: The Molecular Forecaster Approach
Integrating Medicinal Chemistry and Computational Chemistry: The Molecular Forecaster Approach Molecular Forecaster Inc. www.molecularforecaster.com Company Profile Founded in 2010 by Dr. Eric Therrien
More informationAbsorption of Drugs. Transport of a drug from the GI tract
Absorption of Drugs Absorption is the transfer of a drug from its site of administration to the bloodstream. The rate and efficiency of absorption depend on the route of administration. For IV delivery,
More informationHow To Understand The Chemistry Of A 2D Structure
Finding Better Leads using Molecular Fields Sally Rose, Tim Cheeseright, Cresset BioMolecular Discovery Ltd 2D drawings are a ubiquitous representation for molecular structures. Despite this, they provide
More information1 General introduction
General introduction Peptides and peptidomimetics _ 1 1 General introduction 1.1 Peptides and peptidomimetics umerous small and large peptides, which are sequence and length-specific polymers composed
More informationChemical Basis of Life Module A Anchor 2
Chemical Basis of Life Module A Anchor 2 Key Concepts: - Water is a polar molecule. Therefore, it is able to form multiple hydrogen bonds, which account for many of its special properties. - Water s polarity
More informationCheminformatics and its Role in the Modern Drug Discovery Process
Cheminformatics and its Role in the Modern Drug Discovery Process Novartis Institutes for BioMedical Research Basel, Switzerland With thanks to my colleagues: J. Mühlbacher, B. Rohde, A. Schuffenhauer
More informationChemistry Course Descriptions
Chemistry Course Descriptions Please note: Course numbers and descriptions are given based on the UCF course offerings, if available. Courses Offered UCF BCC CFCC DBCC LSCC SCC VCC CHM 1015 (Pre-College
More informationChapter 3. Protein Structure and Function
Chapter 3 Protein Structure and Function Broad functional classes So Proteins have structure and function... Fine! -Why do we care to know more???? Understanding functional architechture gives us POWER
More informationMasters Learning mode (Форма обучения)
Program Title (Название программы): Pharmacology Degree (Степень) Masters Learning mode (Форма обучения) Full-time and part-time Duration of study (Продолжительность программы) 2 years (4 years part time)
More informationComputational Tools for Medicinal Chemists Increasing the Dimensions of Drug Discovery. Dr Robert Scoffin CEO
Computational Tools for Medicinal Chemists Increasing the Dimensions of Drug Discovery Dr Robert Scoffin CE Agenda > Building Desktop Tools - A History > About Cresset BioMolecular Discovery > Fields,
More informationDesigned chemical libraries for hit/lead optimisation
Designed chemical libraries for hit/lead optimisation The integration of high-throughput synthetic chemistry with sophisticated library design technology offers advantages in terms of speed and generality.
More informationOrganic Functional Groups Chapter 7. Alcohols, Ethers and More
Organic Functional Groups Chapter 7 Alcohols, Ethers and More 1 What do you do when you are in Pain? What do you do when you are in a lot of pain? 2 Functional Groups A functional group is an atom, groups
More informationWorking With Enzymes. a world of learning. Introduction. How Enzymes Work. Types and Sources of Enzymes
Working With Enzymes a world of learning Presented by Peter J Ball, Southern Biological. For further information, please contact the author by phone (03) 9877-4597 or by email peterjball@southernbiological.com.
More informationpencil. Vocabulary: 1. Reactant 2. Product 3. Activation energy 4. Catalyst 5. substrate 6. Chemical reaction Keep your textbooks when you are done
Objectives Students will explore the importance of chemical reactions in biology Students will discuss the role of enzymes as catalysts in biological reactions. Students will analyze graphs showing how
More informationCall 2014: High throughput screening of therapeutic molecules and rare diseases
Call 2014: High throughput screening of therapeutic molecules and rare diseases The second call High throughput screening of therapeutic molecules and rare diseases launched by the French Foundation for
More informationCNAS ASSESSMENT COMMITTEE CHEMISTRY (CH) DEGREE PROGRAM CURRICULAR MAPPINGS AND COURSE EXPECTED STUDENT LEARNING OUTCOMES (SLOs)
CNAS ASSESSMENT COMMITTEE CHEMISTRY (CH) DEGREE PROGRAM CURRICULAR MAPPINGS AND COURSE EXPECTED STUDENT LEARNING OUTCOMES (SLOs) DEGREE PROGRAM CURRICULAR MAPPING DEFINED PROGRAM SLOs Course No. 11 12
More informationBIOLOGICAL MEMBRANES: FUNCTIONS, STRUCTURES & TRANSPORT
BIOLOGICAL MEMBRANES: FUNCTIONS, STRUCTURES & TRANSPORT UNIVERSITY OF PNG SCHOOL OF MEDICINE AND HEALTH SCIENCES DISCIPLINE OF BIOCHEMISTRY AND MOLECULAR BIOLOGY BMLS II / B Pharm II / BDS II VJ Temple
More informationCOURSE TITLE COURSE DESCRIPTION
COURSE TITLE COURSE DESCRIPTION CH-00X CHEMISTRY EXIT INTERVIEW All graduating students are required to meet with their department chairperson/program director to finalize requirements for degree completion.
More informationCellular Respiration: Practice Questions #1
Cellular Respiration: Practice Questions #1 1. Which statement best describes one of the events taking place in the chemical reaction? A. Energy is being stored as a result of aerobic respiration. B. Fermentation
More informationChemistry 20 Chapters 15 Enzymes
Chemistry 20 Chapters 15 Enzymes Enzymes: as a catalyst, an enzyme increases the rate of a reaction by changing the way a reaction takes place, but is itself not changed at the end of the reaction. An
More information博 士 論 文 ( 要 約 ) A study on enzymatic synthesis of. stable cyclized peptides which. inhibit protein-protein interactions
博 士 論 文 ( 要 約 ) 論 文 題 目 A study on enzymatic synthesis of stable cyclized peptides which inhibit protein-protein interactions ( 蛋 白 質 間 相 互 作 用 を 阻 害 する 安 定 な 環 状 化 ペプチドの 酵 素 合 成 に 関 する 研 究 ) 氏 名 張 静 1
More informationMULTIPLE CHOICE QUESTIONS
MULTIPLE CHOICE QUESTIONS 1. Most components of energy conversion systems evolved very early; thus, the most fundamental aspects of energy metabolism tend to be: A. quite different among a diverse group
More informationEnzymes: Practice Questions #1
Enzymes: Practice Questions #1 1. Compound X increases the rate of the reaction below. Compound X is most likely A. an enzyme B. a lipid molecule C. an indicator D. an ADP molecule 2. The equation below
More informationChemistry 111 Laboratory Experiment 7: Determination of Reaction Stoichiometry and Chemical Equilibrium
Chemistry 111 Laboratory Experiment 7: Determination of Reaction Stoichiometry and Chemical Equilibrium Introduction The word equilibrium suggests balance or stability. The fact that a chemical reaction
More informationUse of Predictive ADME in Library Profiling and Lead Optimization
Use of Predictive ADME in Library Profiling and Lead Optimization Osman F. Güner and Robert D. Brown 223 rd ACS National Meeting April 2002, Orlando Florida Why Predictive ADME in Early Discovery? The
More informationBiological cell membranes
Unit 14: Cell biology. 14 2 Biological cell membranes The cell surface membrane surrounds the cell and acts as a barrier between the cell s contents and the environment. The cell membrane has multiple
More informationAlterações empresariais sustentadas pelo conceito de engenharia do Produto Patrício Soares da Silva, MD, PhD
Alterações empresariais sustentadas pelo conceito de engenharia do Produto Patrício Soares da Silva, MD, PhD 1 Summary Hypothesis Generation Candidate Development Commercialization Target Identification
More informationCHEMISTRY. Real. Amazing. Program Goals and Learning Outcomes. Preparation for Graduate School. Requirements for the Chemistry Major (71-72 credits)
CHEMISTRY UW-PARKSIDE 2015-17 CATALOG Greenquist 344 262-595-2326 College: Natural and Health Sciences Degree and Programs Offered: Bachelor of Science Major - Chemistry Minor - Chemistry Certificate -
More informationChapter 8 How to Do Chemical Calculations
Chapter 8 How to Do Chemical Calculations Chemistry is both a qualitative and a quantitative science. In the laboratory, it is important to be able to measure quantities of chemical substances and, as
More informationBBSRC TECHNOLOGY STRATEGY: TECHNOLOGIES NEEDED BY RESEARCH KNOWLEDGE PROVIDERS
BBSRC TECHNOLOGY STRATEGY: TECHNOLOGIES NEEDED BY RESEARCH KNOWLEDGE PROVIDERS 1. The Technology Strategy sets out six areas where technological developments are required to push the frontiers of knowledge
More informationAn Introduction to. Medicinal Chemistry
An Introduction to Medicinal Chemistry GRAHAM Oxford University Press, Walton Street, Oxford OX2 6DP Oxford Preface This text is aimed at undergraduates who have a basic grounding in chemistry and are
More information6 Characterization of Casein and Bovine Serum Albumin
6 Characterization of Casein and Bovine Serum Albumin (BSA) Objectives: A) To separate a mixture of casein and bovine serum albumin B) to characterize these proteins based on their solubilities as a function
More informationOrganic Chemistry Calculations
Organic Chemistry Calculations There are three basic units for measurement in the organic laboratory mass, volume, and number, measured in moles. Most of the other types of measurements are combinations
More informationCHM333 LECTURE 13 14: 2/13 15/13 SPRING 2013 Professor Christine Hrycyna
INTRODUCTION TO ENZYMES Enzymes are usually proteins (some RNA) In general, names end with suffix ase Enzymes are catalysts increase the rate of a reaction not consumed by the reaction act repeatedly to
More informationFulvio Gualtieri Department of Pharmaceutical Sciences, University of Florence, Italy
MEDICINAL CHEMISTRY Fulvio Gualtieri Department of Pharmaceutical Sciences, University of Florence, Italy Keywords: Drugs, medicinal chemistry, drug design, drug synthesis, drug development, pharmacokinetics,
More informationEudendron: an Innovative Biotech Start-up
Eudendron: an Innovative Biotech Start-up Mauro Angiolini & Fabio Zuccotto I Venti dell Innovazione, Ville Ponti - Varese, 20 Marzo 2013 Bioindustry Park S. Fumero (Ivrea) - Italy Eudendron: a Quick Description
More informationPerforming Calculatons
Performing Calculatons There are three basic units for measurement in the organic laboratory mass, volume, and number, measured in moles. Most of the other types of measurements are combinations of them,
More informationTraining Courses 2014 HPLC GC SPE
Training Courses 2014 HPLC GC SPE 2 1 3 5 4 6 7 5 10 15 20 min 8 2 Courses & Presenters HPLC How to Run HPLC Methods Price: 249 + VAT Code: SS0-5943 Page: 4 How to Develop HPLC Methods Price: 249 + VAT
More informationCÉLINE LE BAILLY DE TILLEGHEM. Institut de statistique Université catholique de Louvain Louvain-la-Neuve (Belgium)
STATISTICAL CONTRIBUTION TO THE VIRTUAL MULTICRITERIA OPTIMISATION OF COMBINATORIAL MOLECULES LIBRARIES AND TO THE VALIDATION AND APPLICATION OF QSAR MODELS CÉLINE LE BAILLY DE TILLEGHEM Institut de statistique
More informationStem cell research ACADEMY STATEMENT. progress, hopes and concerns ACADEMY STATEMENT 16 JANUARY 2013
ACADEMY STATEMENT 16 JANUARY 2013 ACADEMY STATEMENT Stem cell research progress, hopes and concerns KUNGL. VETENSKAPSAKADEMIEN, BOX 50005, SE-104 05 STOCKHOLM, SWEDEN TEL +46 8 673 95 00, FAX +46 8 15
More informationCHEMISTRY. Faculty. Programs Offered. Bachelor of Science in Chemistry (certified by the American Chemical Society) Careers in Chemistry
CHEMISTRY Department Office Darwin Hall 300 (707) 664-2119 www.sonoma.edu/chemistry Department Chair Lynn R. Cominsky Administrative Coordinator Cathi Cari-Shudde Faculty Steven Farmer Meng-Chih Su *Dale
More informationChemical Bonds and Groups - Part 1
hemical Bonds and Groups - Part 1 ARB SKELETS arbon has a unique role in the cell because of its ability to form strong covalent bonds with other carbon atoms. Thus carbon atoms can join to form chains.
More informationHow to Biotinylate with Reproducible Results
How to Biotinylate with Reproducible Results Introduction The Biotin Streptavidin system continues to be used in many protein based biological research applications including; ELISAs, immunoprecipitation,
More informationData Warehouse Design for Pharmaceutical Drug Discovery Research
Data Warehouse Design for Pharmaceutical Drug Discovery Research Melinda G. Axel and Il-Yeol Song College of Information Science and Technology, Drexel University, Philadelphia., PA, 19104 U.S.A. email:
More informationQuality. Now Certified to ISO 9001:2008
Quality Now Certified to ISO 90012008 Quality Policy It is Peptides International's goal is to achieve complete customer satisfaction by addressing customer needs and delivering what we promise. The company
More informationMolecular Spectroscopy
Molecular Spectroscopy UV-Vis Spectroscopy Absorption Characteristics of Some Common Chromophores UV-Vis Spectroscopy Absorption Characteristics of Aromatic Compounds UV-Vis Spectroscopy Effect of extended
More informationDrug design Drug repositioning Virtual screening
Drug design Drug repositioning Virtual screening May 2013 Plebiotic services Drug design & re-design Drug repositioning Virtual screening Homology modeling Library generation (combinatorial chemistry)
More informationDiabetes and Drug Development
Diabetes and Drug Development Metabolic Disfunction Leads to Multiple Diseases Hypertension ( blood pressure) Metabolic Syndrome (Syndrome X) LDL HDL Lipoproteins Triglycerides FFA Hyperinsulinemia Insulin
More informationCell Biology - Part 2 Membranes
Cell Biology - Part 2 Membranes The organization of cells is made possible by membranes. Membranes isolate, partition, and compartmentalize cells. 1 Membranes isolate the inside of the cell from the outside
More informationKeystone Review Practice Test Module A Cells and Cell Processes. 1. Which characteristic is shared by all prokaryotes and eukaryotes?
Keystone Review Practice Test Module A Cells and Cell Processes 1. Which characteristic is shared by all prokaryotes and eukaryotes? a. Ability to store hereditary information b. Use of organelles to control
More informationA novel method for the synthesis of peptides
A novel method for the synthesis of peptides in solution DioRaSSP (Diosynth Rapid Solution Synthesis of Peptides) offers substantial benefits for the large-scale synthesis of peptides meeting all the specifications
More informationEnergy & Enzymes. Life requires energy for maintenance of order, growth, and reproduction. The energy living things use is chemical energy.
Energy & Enzymes Life requires energy for maintenance of order, growth, and reproduction. The energy living things use is chemical energy. 1 Energy exists in two forms - potential and kinetic. Potential
More informationScoring Functions and Docking. Keith Davies Treweren Consultants Ltd 26 October 2005
Scoring Functions and Docking Keith Davies Treweren Consultants Ltd 26 October 2005 Overview Applications Docking Algorithms Scoring Functions Results Demonstration Docking Applications Drug Design Lead
More informationDe novo design in the cloud from mining big data to clinical candidate
De novo design in the cloud from mining big data to clinical candidate Jérémy Besnard Data Science For Pharma Summit 28 th January 2016 Overview the 3 bullet points Cloud based data platform that can efficiently
More informationChemical reactions allow living things to grow, develop, reproduce, and adapt.
Section 2: Chemical reactions allow living things to grow, develop, reproduce, and adapt. K What I Know W What I Want to Find Out L What I Learned Essential Questions What are the parts of a chemical reaction?
More informationGeneral Properties Protein Nature of Enzymes Folded Shape of Enzymes H-bonds complementary
Proteins that function as biological catalysts are called enzymes. Enzymes speed up specific metabolic reactions. Low contamination, low temperature and fast metabolism are only possible with enzymes.
More informationMolecular descriptors and chemometrics: a powerful combined tool for pharmaceutical, toxicological and environmental problems.
Molecular descriptors and chemometrics: a powerful combined tool for pharmaceutical, toxicological and environmental problems. Roberto Todeschini Milano Chemometrics and QSAR Research Group - Dept. of
More informationCHM333 LECTURE 13 14: 2/13 15/12 SPRING 2012 Professor Christine Hrycyna
INTRODUCTION TO ENZYMES Enzymes are usually proteins (some RNA) In general, names end with suffix ase Enzymes are catalysts increase the rate of a reaction not consumed by the reaction act repeatedly to
More informationHonors Chemistry: Unit 6 Test Stoichiometry PRACTICE TEST ANSWER KEY Page 1. A chemical equation. (C-4.4)
Honors Chemistry: Unit 6 Test Stoichiometry PRACTICE TEST ANSWER KEY Page 1 1. 2. 3. 4. 5. 6. Question What is a symbolic representation of a chemical reaction? What 3 things (values) is a mole of a chemical
More informationAccelerating Lead Generation: Emerging Technologies and Strategies
Brochure More information from http://www.researchandmarkets.com/reports/1057249/ Accelerating Lead Generation: Emerging Technologies and Strategies Description: The number of approvals for new drugs and
More informationWillem Elbers. October 9, 2015
S N 1 and S N 2 reactivity of 3 alkyl bromides Willem Elbers ctober 9, 2015 1 Abstract n this experiment, we investigate the relative reactivities of three alkyl bromides with increasing steric bulk. We
More informationStatistical estimation using confidence intervals
0894PP_ch06 15/3/02 11:02 am Page 135 6 Statistical estimation using confidence intervals In Chapter 2, the concept of the central nature and variability of data and the methods by which these two phenomena
More informationSCIENCE. Introducing updated Cambridge International AS & A Level syllabuses for. Biology 9700 Chemistry 9701 Physics 9702
Introducing updated Cambridge International AS & A Level syllabuses for SCIENCE Biology 9700 Chemistry 9701 Physics 9702 The revised Cambridge International AS & A Level Biology, Chemistry and Physics
More informationCHAPTER 6 AN INTRODUCTION TO METABOLISM. Section B: Enzymes
CHAPTER 6 AN INTRODUCTION TO METABOLISM Section B: Enzymes 1. Enzymes speed up metabolic reactions by lowering energy barriers 2. Enzymes are substrate specific 3. The active site in an enzyme s catalytic
More informationChapter 2: The Chemical Context of Life
Chapter 2: The Chemical Context of Life Name Period This chapter covers the basics that you may have learned in your chemistry class. Whether your teacher goes over this chapter, or assigns it for you
More informationAnatomy and Physiology Placement Exam 2 Practice with Answers at End!
Anatomy and Physiology Placement Exam 2 Practice with Answers at End! General Chemical Principles 1. bonds are characterized by the sharing of electrons between the participating atoms. a. hydrogen b.
More information1. Enzymes. Biochemical Reactions. Chapter 5: Microbial Metabolism. 1. Enzymes. 2. ATP Production. 3. Autotrophic Processes
Chapter 5: Microbial Metabolism 1. Enzymes 2. ATP Production 3. Autotrophic Processes 1. Enzymes Biochemical Reactions All living cells depend on biochemical reactions to maintain homeostasis. All of the
More informationData Visualization in Cheminformatics. Simon Xi Computational Sciences CoE Pfizer Cambridge
Data Visualization in Cheminformatics Simon Xi Computational Sciences CoE Pfizer Cambridge My Background Professional Experience Senior Principal Scientist, Computational Sciences CoE, Pfizer Cambridge
More informationChemistry B11 Chapter 4 Chemical reactions
Chemistry B11 Chapter 4 Chemical reactions Chemical reactions are classified into five groups: A + B AB Synthesis reactions (Combination) H + O H O AB A + B Decomposition reactions (Analysis) NaCl Na +Cl
More informationCarbohydrates, proteins and lipids
Carbohydrates, proteins and lipids Chapter 3 MACROMOLECULES Macromolecules: polymers with molecular weights >1,000 Functional groups THE FOUR MACROMOLECULES IN LIFE Molecules in living organisms: proteins,
More informationPatrick, An Introduction to Medicinal Chemistry 4e Chapter 13 Drug design: optimizing target interactions. Pyrrole ring N H
Patrick, An Introduction to dicinal hemistry 4e hapter 13 Drug design: optimizing target interactions Answers to end-of-chapter questions 1) The pyrrole ring of DU 122290 serves to increase the rigidity
More informationHow to create and interpret the predictive analysis of a compound
How to create and interpret the predictive analysis of a compound Platform with suite of tools Predict & understand biological effects of small molecules & compounds Predict targets and metabolites, potential
More informationWe use Reaxys intensively for hit identification, hit-to-lead and lead optimization.
CASE STUDY Dr. Fabio C. Tucci, COO of Epigen Biosciences We use Reaxys intensively for hit identification, hit-to-lead and lead optimization. CREATING NEW ASSETS Epigen Biosciences is a start-up pharmaceutical
More informationIonization of amino acids
Amino Acids 20 common amino acids there are others found naturally but much less frequently Common structure for amino acid COOH, -NH 2, H and R functional groups all attached to the a carbon Ionization
More informationChemical Bonds. Chemical Bonds. The Nature of Molecules. Energy and Metabolism < < Covalent bonds form when atoms share 2 or more valence electrons.
The Nature of Molecules Chapter 2 Energy and Metabolism Chapter 6 Chemical Bonds Molecules are groups of atoms held together in a stable association. Compounds are molecules containing more than one type
More informationJenn Maeng Lesson overview
Jenn Maeng Lesson overview Subject: Chemistry Grade: 10-12 Topic: Stoichiometry Concepts: Stoichiometric Conversions Essential How do we quantify changes in systems? questions: Objectives Students will
More informationChapter 3 Molecules of Cells
Bio 100 Molecules of cells 1 Chapter 3 Molecules of Cells Compounds containing carbon are called organic compounds Molecules such as methane that are only composed of carbon and hydrogen are called hydrocarbons
More informationgreen B 1 ) into a single unit to model the substrate in this reaction. enzyme
Teacher Key Objectives You will use the model pieces in the kit to: Simulate enzymatic actions. Explain enzymatic specificity. Investigate two types of enzyme inhibitors used in regulating enzymatic activity.
More informationEnzymes. OpenStax College
OpenStax-CNX module: m44429 1 Enzymes OpenStax College This work is produced by OpenStax-CNX and licensed under the Creative Commons Attribution License 4.0 By the end of this section, you will be able
More informationHow To Calculate Mass In Chemical Reactions
We have used the mole concept to calculate mass relationships in chemical formulas Molar mass of ethanol (C 2 H 5 OH)? Molar mass = 2 x 12.011 + 6 x 1.008 + 1 x15.999 = 46.069 g/mol Mass percentage of
More informationCalculating Atoms, Ions, or Molecules Using Moles
TEKS REVIEW 8B Calculating Atoms, Ions, or Molecules Using Moles TEKS 8B READINESS Use the mole concept to calculate the number of atoms, ions, or molecules in a sample TEKS_TXT of material. Vocabulary
More informationProgramme Specification
Programme Specification Awarding Body/Institution Teaching Institution Queen Mary, University of London Queen Mary, University of London Name of Final Award and Programme Title Master in Science (MSci)
More informationDr Alexander Henzing
Horizon 2020 Health, Demographic Change & Wellbeing EU funding, research and collaboration opportunities for 2016/17 Innovate UK funding opportunities in omics, bridging health and life sciences Dr Alexander
More informationBiological molecules:
Biological molecules: All are organic (based on carbon). Monomers vs. polymers: Monomers refer to the subunits that, when polymerized, make up a larger polymer. Monomers may function on their own in some
More informationMaking the most of academic drug target discoveries
Making the most of academic drug target discoveries Richard Reschen, Isis Innovation, University of Oxford The explosion of new technologies and research techniques, and encouragement from funding agencies
More informationLecture 11 Enzymes: Kinetics
Lecture 11 Enzymes: Kinetics Reading: Berg, Tymoczko & Stryer, 6th ed., Chapter 8, pp. 216-225 Key Concepts Kinetics is the study of reaction rates (velocities). Study of enzyme kinetics is useful for
More informationCTC Technology Readiness Levels
CTC Technology Readiness Levels Readiness: Software Development (Adapted from CECOM s Software Technology Readiness Levels) Level 1: Basic principles observed and reported. Lowest level of software readiness.
More informationName Lab #3: Solubility of Organic Compounds Objectives: Introduction: soluble insoluble partially soluble miscible immiscible
Lab #3: Solubility of rganic Compounds bjectives: - Understanding the relative solubility of organic compounds in various solvents. - Exploration of the effect of polar groups on a nonpolar hydrocarbon
More informationEXPERIMENT 5: DIPEPTIDE RESEARCH PROJECT
EXPERIMENT 5: DIPEPTIDE RESEARCH PROJECT Pre-Lab Questions: None. 64 I. Background Information DIPEPTIDE RESEARCH PROJECT Methods developed by organic chemists for the synthesis of biopolymers have had
More informationPeptides: Synthesis and Biological Interest
Peptides: Synthesis and Biological Interest Therapeutic Agents Therapeutic peptides approved by the FDA (2009-2011) 3 Proteins Biopolymers of α-amino acids. Amino acids are joined by peptide bond. They
More informationLead generation and lead optimisation:
Lead generation and lead optimisation: the value of linking HT co-structure analysis and HT chemistry The coupling of High Throughput co-structure analysis with focused library generation is not only proving
More informationWhat affects an enzyme s activity? General environmental factors, such as temperature and ph. Chemicals that specifically influence the enzyme.
CH s 8-9 Respiration & Metabolism Metabolism A catalyst is a chemical agent that speeds up a reaction without being consumed by the reaction. An enzyme is a catalytic protein. Hydrolysis of sucrose by
More information1. 4. 1: Biochemistry of macromolecules and metabolic pathways
1. 4 Investigating enzymes Many factors affect the activity of enzymes and it is very easy to investigate these factors using common enzymes. Enzymes work at their optimum temperature and ph. Any changes
More informationBiological importance of metabolites. Safety and efficacy aspects
Biological importance of metabolites Safety and efficacy aspects Bernard Walther Technologie Servier Biological importance of metabolites Safety testing of drug metabolites Bioanalytical strategy Structural
More informationH H N - C - C 2 R. Three possible forms (not counting R group) depending on ph
Amino acids - 0 common amino acids there are others found naturally but much less frequently - Common structure for amino acid - C, -N, and functional groups all attached to the alpha carbon N - C - C
More informationSingle-celled Organisms and Symbiotic Relationships
and Symbiotic Relationships Lesson Objectives: Students will be able to do the following: Describe an experimental method used by scientists Compare and contrast two studies involving the same symbiotic
More informationHow To Understand The Pharmacology Of The Pharmaceutical Industry
It; MM MODERN Ul NDUSTRY 77 /
More information