Amino Acids carboxylic acid amine R varies with amino acid R = H OH carboxylic acid H2N C H amine  H R R varies with amino acid R = H glycine

R-groups Nonpolar glycine -H alanine -CH3 valine -CH-CH3 CH3 proline 2o amine leucine -CH2-CH-CH3 CH3 phenylalanine isoleucine -CH-CH2-CH3 CH3 methionine -CH2-CH2-S-CH3

Polar R-groups serine -CH2-OH asparagine -CH2-C-NH2 O threonine -CH-CH3 OH glutamine -CH2-C-NH2 O -CH2 tyrosine tryptophan cysteine -CH2-SH

Acidic R-groups -CH2-CH2-C = O OH glutamic acid -CH2-C = O OH aspartic acid

Basic R-groups = lysine -CH2-CH2-CH2-CH2-NH2 arginine -CH2-CH2-CH2-NH-C-NH2 = NH histadine

Amino acids glycine non-chiral all other -amino acids in proteins H2N H O OH R O- H3N+ H R glycine non-chiral all other -amino acids in proteins L-enantiomers at neutral pH (pH = 7.0) zwitterion very high b.p. (> 200oC) very soluble in water

acid-base chemistry low pH neutral pH high pH amine protonated OH R C H2N H O OH R C H2N H O O- R O- H3N+ low pH neutral pH high pH amine protonated amine and c.a. deprotonated amine and c.a. protonated c.a. deprotonated no net charge negative charge positive charge pH = pHI isoelectric point amino acids diprotic acids 2 pKa

Titration of an amino acid alanine R = CH3 C H3N+ H O OH R pKa1 = 2.34 pKa2 = 9.69 Ka1 = 10-2.34 = 4.57 x 10-3 CH3 Ka1 = [H+][A-] [H+] [A-] [HA] 0.1 M [HA] initial 0.1 change +x +x -x equil. 4.57 x 10-3 = x2 +x +x 0.1-x 0.1 - x pH = 1.87 X = 2.14 x 10-2 = [H+]

× net charge pH equivalents of OH- +1 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 ×

× × pH equivalents of OH- net charge 0.05 M 0.05 M 0.05 M pH = pKa + 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 × net charge +1 +1/2 0.05 M pKa1 = 2.34 0.05 M 0.05 M × pH = pKa + log [A-] [HA] 0.05 M 1/2 pH = pKa = 2.34

× × net charge at equivalence point: pH isoelectric point pH = +1 +1/2 pKa2 = 9.69 pKa1 = 2.34 pH equivalents of OH- 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 × × isoelectric point pH = pKa1 + pKa2 2 pH = (2.34 + 9.69)/2 1/2 1 pH = pHI = 6.02

× × × × pH equivalents of OH- net charge at 2nd half-way point: 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 × net charge at 2nd half-way point: +1 +1/2 -1/2 -1 × × pKa2 = 9.69 × pH = pKa2 = 9.69 1/2 1 3/2

amides resonance structure dipeptide alanine glycine Ala-Gly +H2O

Proteins _ “backbone” _ H _ R _ H _ R _ H _ R H N1- C1- C1- N2- C2- OH = O = O = O peptide bonds C-terminal residue N-terminal residue biological activity = structure protein structure 4 levels Primary structure = order of the amino acids

Secondary structure hydrogen bonding backbone groups N1- C1- C1- N2- _ H = O OH R H-bond donors H-bond acceptors Two main secondary structures: -helix -sheet

Alpha helix = = Every C=O bonded to N-H 4 residues away forms a helix core is backbone R-groups outside 3.6 amino acids per turn C = O N H proline no H-bonding breaks helix = O C

Beta sheet Every C=O bonded to N-H far apart in 1o structure on different chains peptide chains extended side-by-side maximal H-bonding for anti-parallel chains small R-groups above and below the sheet if not -helix or -sheet random coil

= glutamic acid R = - CH2CH2COOH pKa1 = 3.20 (-COOH) pKa2 = 4.25 H3N+ H O OH R pKa1 = 3.20 (-COOH) CH2CH2C = O OH pKa2 = 4.25 (R-COOH) pKa3 = 9.67 (-NH3) It will take ___ equivalents to titrate glutamic acid 3 1st group 2nd group 3rd group

= × × × × × pKa1 = 3.20 pKa2 = 4.25 pHI = 3.7 pKa3 = 9.67 3.2 + 4.25 O -2 +1 -1 C 12 OH H3N+ C H = O 10 × CH2CH2C OH 8 pKa1 = 3.20 × pH pKa2 = 4.25 pHI = 3.7 pKa3 = 9.67 × 4 × × 3.2 + 4.25 = 3.7 2 2 4.25 + 9.67 = 7.0 2 1 2 3 equivalents OH-