Exploring metal-driven stereoselectivity of glycopeptides by free-energy calculations*

摘要

A formalism to quantify the chemical stereoselectivity, based on free energy of binding calculations, is here discussed. It is used to explain the stereoselectivity of two diastereoisomeric frameworks, comprising the dimer of a copper(II)-peptide core of L- and D-carnosine, respectively, each bound to two chains of D-trehalose, in which copper(II) adopts a type-II coordination geometry. The stereocenter of carnosine is varied both L and b, giving rise to two diastereoisomers. A thermodynamic cycle crossing the formation of the two enantiomeric copper(II) peptide cores was devised. A harmonic restraining potential that depends only on the bond distance was added to ensure reversibility in bond formation and dissociation, for an accurate estimate of the free energy. The calculation of the free energy of binding between D-trehalose and the two enantiomeric copper(II) peptide cores reproduces the free-energy quantities observed from stability constants and isothermal titration calorime-try (ITC) measurements. This is an example of chirality selection based on free-energy difference.