Noncovalent Interactions between Unsolvated Peptides: Dissociation of Helical and Globular Peptide Complexes

Abstract

The thermally activated unimolecular dissociation of some unsolvated complexes of helical and globular alanine/glycine-based peptides have been studied by electrospray mass spectrometry and ion mobility measurements. Rate constants have been measured as a function of temperature, and activation energies and entropies have been determined for dissociation of the Ac-(GA)7K·Ac-A(GA)7K + 2H+ (Ac = acetyl, G = glycine, A = alanine, and K = lysine) dimer (dominant conformation assigned to a V-shaped helical dimer) and the 2Ac-(GA)7K·Ac-A(GA)7K + 3H+ and Ac-(GA)7K·2Ac-A(GA)7K + 3H+ trimers (dominant conformation assigned to a pinwheel-shaped helical trimer). The activation energies were found to be 91 kJ mol-1 for the dissociation of the dimer, and 72 and 77 kJ mol-1 for dissociation of the trimers. A key advantage of the experimental approach described here is that it permits the conformations of the dissociating peptides to be observed. For the Ac-K(GA)7·Ac-KA(GA)7 + 2H+ dimer (which has the lysines at the N-terminus), there are two major conformations present (assigned to a compact globular aggregate and an antiparallel helical dimer) which appear to dissociate with different rates. The Ac-K(GA)7·Ac-KA(GA)7 + 2H+ dimers dissociate at a significantly higher temperature than the V-shaped Ac-(GA)7K·Ac-A(GA)7K + 2H+ dimer. The alanine analogue of the antiparallel helical dimer, Ac-KA14·Ac-KA15 + 2H+, does not dissociate significantly at the highest temperature accessible (∼423 K).