Combinatorial Synthesis of Highly Selective Cyclohexapeptides for Separation of Amino Acid Enantiomers by Capillary Electrophoresis

Abstract

Cyclic peptide libraries dissolved in the electrolyte solution can be used as chiral selectors in capillary electrophoresis. In the present investigation, the resolution obtained in capillary electrophoresis for a set of dinitrophenyl-d,l-amino acids was the parameter used to screen for the most effective selectors contained in a mixture of thousands of components of a cyclic hexapeptide sublibrary with three randomized positions. The deconvolution procedure was simplified by fractionating the sublibrary components according to the hydrophobicity of the amino acids in the randomized positions through reversed-phase HPLC. By comparing the resolution obtained with the separated fractions, a set of hydrophobic amino acids was recognized as essential to achieve adequate enantioselectivity. The whole deconvolution process, which made it possible to select two highly selective cyclopeptides, required the synthesis and the evaluation of 15 sublibraries instead of the 54 syntheses required by a classical procedure of serial deconvolution.