On-resin cyclization and antimicrobial activity of Laterocidin and its analogues

Total synthesis of cyclodecapeptide antibiotics from Bacillus laterosporus, laterocidin and its analogues, was accomplished for the first time by solid-phase peptide synthesis followed by traceless on-resin cyclization of the linear precursors with protection of α-carboxyl group on the Asp residue by Dmab as a temporary blocking group for on-resin head-to-tail cyclization, in which the carboxyl group of side chain of Asp was linked to Rink resin. Single alanine substitution or Asn substitution (Asp¹⁰→Asn¹⁰) demonstrated improvements in antibacterial activity. Of note, d-Phe² and Pro⁴ play an important role in on-resin head-to-tail cyclization and exerting antibacterial activity of Laterocidin.