Harpers

AMINO ACIDS & PEPTIDES / 19rosyl). Peptides are then named as derivatives of thecarboxyl terminal aminoacyl residue. For example, Lys-Leu-Tyr-Gln is called lysyl-leucyl-tyrosyl-glutamine.The -ine ending on glutamine indicates that its α-carboxylgroup is not involved in peptide bond formation.CH 2OCNSHCH 2 HCH NC CH 2Peptide Structures Are Easy to DrawPrefixes like tri- or octa- denote peptides with three oreight residues, respectively, not those with three oreight peptide bonds. By convention, peptides are writtenwith the residue that bears the free α-amino groupat the left. To draw a peptide, use a zigzag to representthe main chain or backbone. Add the main chain atoms,which occur in the repeating order: α-nitrogen, α-carbon,carbonyl carbon. Now add a hydrogen atom toeach α-carbon and to each peptide nitrogen, and anoxygen to the carbonyl carbon. Finally, add the appropriateR groups (shaded) to each α-carbon atom.N C C α N CC α N C C αO H 3 C H+ H3 N C CC N CHHCH 2O– OOCHN COO –CH CH 2Three-letter abbreviations linked by straight linesrepresent an unambiguous primary structure. Lines areomitted for single-letter abbreviations.Glu - Ala - Lys - Gly - Tyr - AlaE A K G Y AWhere there is uncertainty about the order of a portionof a polypeptide, the questionable residues are enclosedin brackets and separated by commas.Glu -Lys -( Ala, Gly, Tyr)-His -AlaSome Peptides Contain UnusualAmino AcidsIn mammals, peptide hormones typically contain onlythe α-amino acids of proteins linked by standard peptidebonds. Other peptides may, however, contain nonproteinamino acids, derivatives of the protein aminoacids, or amino acids linked by an atypical peptidebond. For example, the amino terminal glutamate ofglutathione, which participates in protein folding andin the metabolism of xenobiotics (Chapter 53), islinked to cysteine by a non-α peptide bond (Figure3–3). The amino terminal glutamate of thyrotropin-OHHCH H2O COO –+C NH 3COO –Figure 3–3. Glutathione (γ-glutamyl-cysteinylglycine).Note the non-α peptide bond that linksGlu to Cys.releasing hormone (TRH) is cyclized to pyroglutamicacid, and the carboxyl group of the carboxyl terminalprolyl residue is amidated. Peptides elaborated by fungi,bacteria, and lower animals can contain nonproteinamino acids. The antibiotics tyrocidin and gramicidin Sare cyclic polypeptides that contain D-phenylalanineand ornithine. The heptapeptide opioids dermorphinand deltophorin in the skin of South American treefrogs contain D-tyrosine and D-alanine.Peptides Are PolyelectrolytesThe peptide bond is uncharged at any pH of physiologicinterest. Formation of peptides from amino acids istherefore accompanied by a net loss of one positive andone negative charge per peptide bond formed. Peptidesnevertheless are charged at physiologic pH owing to theircarboxyl and amino terminal groups and, where present,their acidic or basic R groups. As for amino acids, the netcharge on a peptide depends on the pH of its environmentand on the pK a values of its dissociating groups.The Peptide Bond Has PartialDouble-Bond CharacterAlthough peptides are written as if a single bond linkedthe α-carboxyl and α-nitrogen atoms, this bond in factexhibits partial double-bond character:OCNHThere thus is no freedom of rotation about the bondthat connects the carbonyl carbon and the nitrogen of apeptide bond. Consequently, all four of the coloredatoms of Figure 3–4 are coplanar. The imposed semirigidityof the peptide bond has important conse-O –CN +H