Amino Acid Titration At physiological pH, the carboxyl group of the AA

Amino Acid Titration At physiological pH, the carboxyl group of the AA is negatively charged and the amino group is positively charged. Amino acids without charged side chains are zwitterions and have no net charge. H3 N-CHR-COO-. A titration curve shows how the amine and carboxyl groups react with hydrogen ion. 5P1-1

Amino Acid Titration-2 At low pH a nonacidic/nonbasic amino acid is protonated and has the structure below. H3N CHRCOOH The charge behavior of acidic and basic AAs is more complex. 5P1-2

Titration of Alanine B C pK2 9.73 10 C O H3N CHC OH R1 A O H3N CH C O R1 B O H3N CH1C O R1 C pH 5 1 B, pI pH 6.0 A A B pK1 2.3 1 mole base added 2 5P1-3

Isoelectric point The isoelectric point (pI) for an AA occurs when there is no net charge. For a neutral AA, the pI is calculated using the equation pK1 pK2/2 Eg.: alanine: 2.34 9.7 / 2 6.0 For acidic or basic AAs, the pI is the average of the two pKa values bracketing the isoelectric structure. 5P1-4

Isoelectric point-2 In general the pI is the average of the two pKa’s bracketing the isoelectric structure. Eg.: glutamic acid, pI 3.2 pK3 9.9 pK2 4.3 pK1 2.2 5P1-5

5.2 Peptides Peptide: a polymer of about 2-100 AAs linked by the peptide(amide) bond. As the amino group and the carboxyl group link, water is lost. H H O H O O H3N C C O H3N C C O H3N C C O R1 -H2O R1 -H2O R1 H O H O H O H3N C C N C C N C C O H H R1 R1 R1 Peptide bonds 5P1-6

Peptides-2 A peptide is written with the N-terminal end to the left and the C-terminal end to the right. H2N-Tyr-Ala-Cys-Gly-COOH Name Tyrosylalanylcysteinylglycine The peptide bond is rigid and planar due to the resonance contribution shown right. C C H H C N C N C C - O O 5P1-7

Peptides-3 The peptide bond angles force specific conformations of proteins and, on extended chains, successive R groups are on opposite sides. 5P1-8

Physiologically Interesting Peptides carbon O H3N CH2CH2C NH CH COO - -alanyl-L-histidine CH2 HC C NH N C Common name: carnosine found in muscle tissue 5P1-9

Physiologically Interesting Peptides - COO O O - H3N CH CH2 CH2 C NH CH C NH CH2COO CH2 SH -glutamyl-L-cysteineylglycine Glutathione: the reduced form reduces oxidizing agents by dimerizing to form the disulfide bond with release of 2 H. 5P1-10

Physiologically Interesting Peptides Tyr-Gly-Gly-Phe-Leu N-terminal AA C-terminal AA Short form description for a peptide. Leucine enkephalin: a natural analgesic found in the brain 5P1-11

Physiologically Interesting Peptides H3 3 N -Cys-Tyr-Ile Oxytocin Induces labor and aids in forcing milk from the mammary glands. S Gln S -Cys-Asn 8 Pro-Leu-Gly-NH2 Vassopressin has a Phe at position 3 instead of Ile and an Arg at position 8 instead of a Leu. Its role is in regulating blood pressure. 5P1-12