Kinetics of amide proton exchange in helical peptides of varying chain lengths. Interpretation by the Lifson-Roig equation

Abstract

The kinetics of amide proton exchange (1H----2H) have been measured by proton nuclear magnetic resonance spectroscopy for a set of helical peptides with the generic formula Ac-(AAKAA)m Y-NH2 and with chain lengths varying from 6 to 51 residues. The integrated intensity of the amide resonances has been measured as a function of time in 2H2O at pH* 2.50. Exchange kinetics for these peptides can be modeled by applying the Lifson-Roig treatment for the helix-to-coil transition. The Lifson-Roig equation is used to compute the probability that each residue is helical, as defined by its backbone (phi, psi) angles. A recursion formula then is used to find the probability that the backbone amide proton of each residue is hydrogen bonded. The peptide helix can be treated as a homopolymer, and direct exchange from the helix can be neglected. The expression for the exchange kinetics contains only three unknown parameters: the rate constant for exchange of a non-hydrogen-bonded (random coil) backbone amide proton and the nucleation (v2) and propagation (w) parameters of the Lifson-Roig theory. The fit of the exchange curves to these three parameters is very good, and the values for v2 and w agree with those derived from circular dichroism studies of the thermally-induced unfolding of related peptides [Scholtz, J.M., Qian, H., York, E.J., Stewart, J.M., & Baldwin, R.L. (1991) Biopolymers (in press]).