Amino Acids. base MeNH 2. H 3 NMe conjugate base. conjugate acid. R O H acid. base NH 2 R 1 R H acid

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1 Amino Acids 1 The basic amine reacts with the acidic proton of acetic acid to form a conjugate base and a conjugate acid. If methylamine and acetic acid ( = C 3 ) are mixed together, for example, the product is methylammonium acetate, 43. Amino acid 44 reacts with the carboxylic acid unit in exactly the same way, but the acid-base reaction is an internal reaction that gives 45, with a positively charged ammonium unit (- 3+ ) and a negatively charged carboxylate unit (-C 2 ) in the same molecule. Such molecules are known as dipolar ionic molecules or zwitterions. acid base Me 2 base 2 acid 43 3 Me conjugate base conjugate acid 3 conjugate base conjugate acid

2 Amino Acids Zwitterion 45 reacts with aqueous acid in a similar manner to give 46. These are acid-base reactions, so an equilibrium is shown between 46, 45, and Cl Cl aac Cl a 1 2 Ac + acl 2 2 C 2 C K 2 1 K C 2 K 1 = [45] [46] K 2 = [47] [45]

3 Amino Acids: Isoelectric Point 3 If one equivalent of base is added to 46, removal of the most acidic proton (the carboxyl proton) gives zwitterion 45. When exactly one equivalent of base has been added, the zwitterion form (45) is the species in solution. The p of the solution at exactly this point is called the isoelectric point. As the 1 and 2 groups are changed, each new compound may have a different pk 1 value. As a practical matter, this means the isoelectric point for each different amino acid will change in relation to its structure. p C 2 2 pk 1 isoelectric point Equivalents of base C 2 3 pk C 2 2

4 Amino Acids: D and L 4 There is a carbohydrate called glyceraldehyde [C 2 C()C], which is drawn in Fischer projection and also as the usual line notation. Fischer s nomenclature system draws structures in what we now call a Fischer projection. Using this system, Fischer assigned the structure of (+)-glyceraldehyde as 48, with the C unit on "top" and the unit on the "right," as shown. The distinguishing unit is on the right (dexter in Latin) Fischer called this a D-configuration, and 48 is D-(+)-glyceraldehyde. The other enantiomer is drawn as 49, with the unit on the left (lever in Latin) and this is a L-configuration. C C 2 D-(+)-glyceraldehyde C C 2 49 Therefore, 49 is L-( )-glyceraldehyde. 2 C C C C 2 C C 2 48 C C 2 L-(-)-glyceraldehyde

5 Amino Acids: D and L 5 There are two enantiomers for each amino acid, based on the zwitterionic forms of the amino acid (with one alkyl group and one hydrogen atom). Stereoisomers 50 and 51 as drawn in Fischer projection and also as the analogous line drawing. In the Fischer projections, the C unit is on the "top" just as the C unit is on top in glyceraldehyde. If the nitrogen group is on the "right" it is a D-amino acid (50) whereas an L-amino acid has the 3 unit on the left (51). 3 () C 2 3 C 2 () C 2 () 3 3 C () C C 2

6 Amino Acids: Essential 6 Me CMe 2 CMe 2 C(Me)Et C 2 Ph C 2 C()Me C 2 (4-hydroxy-C 6 4 ) C 2 S C 2 C 2 SMe C 2 C 2 C 2 C 2 C 2 C 2 C C 2 C 2 C C 2 C 2 C 2 C 2 2 C 2 (2-indolyl) C 2 (4-imidazolyl) C 2 C(=) 2 2-pyrrolidinyl 3 C 2 3 C 2 50 glycine (52) alanine (53) valine (54) leucine (55) isoleucine (56) phenylalanine (57) serine (58) threonine (59) tyrosine (60) cysteine (61) methionine (62) asparagine (63) glutamine (64) aspartic acid (65) glutamic acid (66) lysine (67) tryptophan (68) histidine (69) arginine (70) proline (73) C 2 3 ame Three Letter Code ne-letter Code gly ala val leu ile phe ser thr tyr cys met asn gln asp glu lys trp his arg pro G A V L I F S T Y C M Q D E K W P

7 C 2 Functionalized Amino Acids and pk C 2 C 2 7 glycine K 1 3 K 3 K glutamic acid C 2 C 2 C 2 C 2 K 1 K 2 K tyrosine C 2 C 2 C 2 C 2 2 lysine 3 C 2 2 K 1 3 C 2 3 K 2 2 pk 3 measures the acidity of the side chain acid, but does not necessarily indicate the position of that step in the equilibrium for a given amino acid. C 2 2 K 3 2 C 2

8 Amino Acids: Synthesis 8 The Strecker synthesis. If an aldehyde reacts with ammonia in the presence of C, an amino nitrile is formed. Acid hydrolysis of the nitrile unit gives an amino acid. C! 3, C aq. + C 2 Me 2 Me Me ther routes Br 3 Ph C 2 Br 2 3 C PBr 2 heat Ph Ph C 2 An α-bromo acid is prepared by the ell- Volhard-Zelenskii reaction. Cl 3 3 C 2 heat C 2

9 Amino Acids: Synthesis 9 Et 2 C C 2 Et PBr Br 2 Br K K Et 2 C 101 C2Et C 2 Et C 2 Et C 2 Et C a 2 Et a C 2 Et C 2 Et Ph Ph C PhC 2 Br 2 Et 3 + C 2 - C 2 C 2 Et C 2 C 2

10 Peptides 10 Polyamides derived from amino acids are known as peptides, and the amide bonds within the peptide are called peptide bonds. Both 122 and 123 are composed of two amino acids, so they are called dipeptides. ligopeptide: generally 2-25 amino acids A peptide with three amino acid units is a tripeptide and a peptide with fifteen amino acid units is called a pentadecapeptide. The amino acid components of a peptide are known as amino acid residues,, so 122 or 123 have two amino acid residues, and a decapeptide has ten amino acid residues 1 C C C C 2

11 Peptide Bond 11 An amide (peptide) bond connects two amino acid residues and it is essentially planar. Structure 125 shows an amide bond fragment and the electrons are delocalized as shown by the two resonance structures, 125A and 125B. This delocalization leads to the C- unit having "partial doublebond character," which is normal for the C- unit in simple amides A 125B

12 Peptide Bond There is rotation about the C- bond (between the carbonyl carbon and the nitrogen. The groups on carbon and nitrogen trans- to each other is lower in energy than the arrangement of groups in conformations resulting from the other rotational angles. The amide unit is essentially planar, and the groups attached to the carbonyl and the nitrogen may have different stereochemical relationships, and the relationship will vary with the nature of the groups. 12

13 Peptide Bond 13 The rotational angle for the C α C= bond is labeled by ψ, which is the angle defined by rotation about that bond. The C α is the carbon of the amino acid that bears the substituent (methyl, isopropyl, hydroxymethyl, etc). The angle φ is defined as the angle for rotation about the C α bond. C 3 2!! " " 126A! rotational angle!, C C= "! " "! 126B rotational angle ", C