Solid-phase synthesis and antibiotic activities of cyclodecapeptides on the scaffold of naturally occurring Laterocidin.
The development of new antibacterial therapeutic agents capable of halting microbial resistance is a chief pursuit in clinical medicine. Laterocidin and its analogues were synthesized for the first time by solid-phase synthesis method via linking of the carboxyl group on side chain of Aspartate to Rink resin with the protection of side chain alpha-carboxyl group of Aspartate by Dmab as a temporary alpha-COOH protecting group for the on-resin cyclization. Different configuration of N- and C-terminal was benefit to peptide cyclization. Laterocidin analogue 3 (Asp(1)-->Asn(1), Phe(4)-->Tyr(4) and d-Tyr(6)-->d-Phe(6)) demonstrated potent and broad antimicrobial properties, especially exhibited activity against clinical Methicillin-resistant Staphylococcus aureus (L-MRSA) and the gram-negative extended-spectrum beta-lactamases-producing Escherichia coli (ESBLs E. coli) and L-E.coli. This finding has important significance to exploit new antibiotic medicine.
Xu
Chunlan
C
Faculty of Life Science, Northwestern Polytechnical University, Xi'an 710072, PR China.
Qin
Chuanguang
C
Zhang
Ruijie
R
Niu
Weining
W
Shang
Xiaoya
X
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D010456:Peptides, Cyclic