Proline cis-trans isomerization and its implications for the dimerization of analogues of cyclopeptide stylostatin 1: a combined computational and experimental study.

Cis and trans proline conformers are often associated with dramatic changes in the biological function of peptides. A slow equilibrium between cis and trans Ile-Pro amide bond conformers occurs in constrained derivatives of the native marine cyclic heptapeptide stylostatin 1 (cyclo-(NSLAIPF)), a potential anticancer agent. In this work, four cyclopeptides, cyclo-(NSTAIPF), cyclo-(KSTAIPF), cyclo-(RSTAIPF) and cyclo-(DSTAIPF), which are structurally related to stylostatin 1, are experimentally and computationally examined in order to assess the effect of residue mutations on the cis-trans conformational ratio and the apparent capacity to form dimeric aggregates.

Enhanced reactivity of Lys182 explains the limited efficacy of biogenic amines in preventing the inactivation of glucose-6-phosphate dehydrogenase by methylglyoxal.

This study examines the inactivation of the enzyme glucose 6-phosphate dehydrogenase (G6PD) by methylglyoxal (MG) and the eventual protection exerted by endogenous amines. To determine the protective effect of amines, the rate constant of the reaction of MG with the amino group of N-α-acetyl-lysine, carnosine, spermine and spermidine was measured at pH 7.4, and the behavior of endogenous amines was analyzed on the basis of quantum chemical reactivity descriptors.