Solution Conformation of Cyclo(D-Leu-L-Glu-L-His)2 and Its Relation with Highly Efficient and Enantiomer-Selective Catalysis

Abstract

A cyclic hexapeptide cyclo(D-Leu-L-Glu-L-His)2 was synthesized and its conformational properties in (CD3)2SO and D2O were investigated. The major conformation in (CD3)2SO was asymmetric and possessed either a gramicidine-type β-turn structure or a random structure in one molecule. The major conformation in D2O was a C2-symmetric random structure. When Cu(ClO4)2 was added to an aqueous solution of cyclo(D-Leu-L-Glu-L-His)2 (pH 6.95, phosphate buffer), the major conformation of the latter changed from a random to a type-II β-turn structure. The cyclic hexapeptide/Cu2+ molar ratio of the complex was unity, and Cu2+ was coordinated with Glu-COOH. Induced by copper-ion coordination the backbone plane, the Leu-isobutyl group, and the His-imidazolylmethyl group of cyclo(D-Leu-L-Glu-L-His)2 had the form of a hydrophobic pocket. The highly efficient hydrolysis of leucine or valine p-nitrophenyl ester hydrochloride by the cycloD-Leu-L-Glu-L-His)2–Cu2+ complex may be closely related to the binding of a substrate by the hydrophobic pocket. The weak enantiomer-selectivity may also be related to a streochemical fit of a bound substrate with the hydrophobic pocket.