Solid-phase synthesis of 5-arylhistidine-containing peptides with antimicrobial activity through a microwave-assisted Suzuki-Miyaura cross-coupling

Abstract

A microwave-assisted solid-phase Suzuki-Miyaura reaction has been employed for the synthesis of 5-arylhistidine-containing peptides. In particular, sequences containing a 5-arylhistidine at the 1- or 4-positions have been designed based on lead antimicrobial peptides. The cross-coupling involved the arylation of a resin-bound 5-bromohistidine with an arylboronic acid in solution under microwave irradiation. This protocol is compatible with common protecting groups used in peptide chemistry. The resulting biaryl linear undecapeptides were screened for their antibacterial, antifungal and hemolytic activities. The results showed that the presence of an imidazole ring significantly decreases the cytotoxicity. A solid-phase Suzuki-Miyaura reaction has been applied to the synthesis of 5-arylhistidine undecapeptides. The biaryl peptides displayed low hemolytic antimicrobial activity