Enzymatic synthesis of N-protected amino acid-steroid derivatives in organic solvent

Abstract

Peptidyl steroids are compounds in which amino acids or peptides are coupled with steroids by amide or ester bonds. Cholyl glycine and cholyl taurine are such analogs found in humans. Previously, we synthesized a new series of amino acid and peptide derivatives of estradiol using different coupling reagents, and studied their binding affinities [1]. Recently, significant progress has been made in the field of enzymatic peptide synthesis [2]. We synthesized a series of peptide derivatives such as Nprotected Leu-enkephalin in organic solvents using several peptidyl proteases [3]. The advantages of enzymatic synthesis include mild reaction conditions, no racemation, minimal side-chain protection, and high regioand stereoselectivity. In the current study, we report the successful synthesis of the N-protected amino acid-estrone derivatives using subtilisin Carlsberg as the catalyst in organic solvent for the first time. The influences of different protecting groups and esters in the carboxyl component on the enzymatic reaction were compared.