STUDIES OF NEAREST-NEIGHBOR INTERACTIONS BETWEEN AMINO-ACIDS IN GAS-PHASE PROTONATED PEPTIDES

The probe of intramolecular interactions in gas-phase biomolecules usi ng the combination of proton transfer reactions, hydrogen/deuterium ex change reactions, and molecular orbital calculations is illustrated by exploring the nearest-neighbor interactions in protonated peptides. T he interactions, specifically -NH2 ... H+... O=C and C=O ... H+... O=C , are investigated with peptides that model them. The compounds that i nclude beta-Ala, beta-Ala-Gly, and Gly-beta-Ala, Ala-Gly and Gly-Ala a re used to evaluate the structural and electronic factors that are inv olved in the protonation of the terminal amine. Similarly, N-acetylgly cine and N-acetylglycine amide are used to evaluate carbonyl group int eractions in the peptide backbone. The beta-alanine residue on the ter minal amine is found to increase the gas-phase basicity and decrease t he H/D exchange reactivity of the protonated compound relative to anal ogous compounds containing only alpha-amino acids. A beta-alanine resi due on the C-terminus produces compounds with similar gas-phase basici ty and H/D exchange behavior as those with alpha-amino acids. The gas- phase basicity and H/D exchange behavior of the acetylglycines point t o stronger intramolecular hydrogen bonding in the amide derivative tha n in the acid. An amide carbonyl has a greater intrinsic basicity than a carboxylic carbonyl. An analysis proposed by Meot-Ner is used to se parate electronic effects from structural effects in the two types of protonation sites.