Chem 109 C Fall 2014 Armen Zakarian ffice: Chemistry Bldn 2217! http://web.chem.ucsb.edu/~zakariangroup/courses.html! 1
Amino acids: Resolution of Racemates 2
Peptides/Proteins: Peptide Bonds - - - - peptides: formed from simple amino acids through peptide bonds 3
Peptides/Proteins: Peptide Bonds - - - - peptides: formed from simple amino acids through peptide bonds - 4
Peptides/Proteins: Peptide Bonds - - - - peptides: formed from simple amino acids through peptide bonds - - 5
Peptides/Proteins: Peptide Bonds - - - - peptides: formed from simple amino acids through peptide bonds -terminal aa C-terminal aa - - 6
Peptides/Proteins: Peptide Bonds - - - - peptides: formed from simple amino acids through peptide bonds -terminal aa C-terminal aa - - if sequence known Phe-Ser-Leu-Leu FSLL Leu-Ser-Phe-Leu LSFL 7
Peptides/Proteins: Peptide Bonds - - - - peptides: formed from simple amino acids through peptide bonds -terminal aa C-terminal aa - - if sequence known Phe-Ser-Leu-Leu FSLL Leu-Ser-Phe-Leu LSFL if sequence unknown Leu, Phe, Ser Leu, Phe, Ser 8
Peptides/Proteins: Peptide Bonds!-carbon R - R + R R peptide bond: about 40% double bond character restricted rotation s-trans is more stable R R R R s-trans strongly FAVRED s-cis strongly disfavored 9
Peptides/Proteins: Peptide Bonds colored squares - planar where is free rotation? 10
Peptides/Proteins: Peptide Bonds PRBLEM 24 Draw the tetrapeptide Ala-Thr-Asp-Asn and indicate the peptide bonds 11
Peptides/Proteins: Peptide Bonds PRBLEM Using the three-letter abbreviations, write the six tripeptides consisting of Ala, Gly, and Met. 12
Peptides/Proteins: Disulfide Bonds mild oxidant 2 R S R S S R a thiol a disulfide disulfide bridge 13
Peptides/Proteins: Disulfide Bonds 14
Peptides/Proteins: Some Interesting Peptides endorphines: 15
Peptides/Proteins: Some Interesting Peptides endorphines: fight-or-flight hormone: Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly- 2 S S vasopressin 16
Peptides/Proteins: Some Interesting Peptides endorphines: fight-or-flight hormone: Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly- 2 social bonding hormone: S S vasopressin Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly- 2 S S oxytocin 17
-protection C-activation 18
-protection C-activation 1. 2. 3. 19
Making Gly-Ala Step 1. Protect of Gly 20
Making Gly-Ala Step 1. Protect of Gly Step 2. Activating -protected Gly 21
Making Gly-Ala Step 1. Protect of Gly Step 2. Activating -protected Gly Step 3. Adding Ala 22
Making Gly-Ala Step 1. Protect of Gly Step 2. Activating -protected Gly Step 3. Adding Ala Step 4. Deprotection - mission completion 23
overall yield for the attachment of amino acids: number of amino acids 2 3 4 5 6 7 8 9 overall yield 80% 64% 51% 41% 33% 26% 21% 17% 24
PRBLEM Show the steps in the synthesis of Leu-Phe-Lys-Val 25
PRBLEM Calculate the overall yield of bradykinin when the yield for the addition of each amino acid to the chain is 70%. Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg! 26
Merrifield automated synthesis 27
Merrifield automated synthesis 28
Merrifield automated synthesis 29
Merrifield automated synthesis 30
Merrifield automated synthesis 31
Merrifield automated synthesis 32
Merrifield automated synthesis 33
Merrifield automated synthesis 34
Merrifield automated synthesis 35
Merrifield automated synthesis 36
Merrifield automated synthesis 37
Merrifield automated synthesis overview of the Merrifield automated synthesis: synthesis on solid support, >98% yield per a.a. C to terminus nonapeptide bradykinin synthesized in 4 h and 85% overall yield limitation: up to a 100 amino acids 38