Title: Solid-phase synthesis of polymyxin B1 and analogues via a safety-catch approach
Authors: de Visser, P C ×
Kriek, N M A J
van Hooft, P A V
Van Schepdael, Ann
Filippov, D V
van der Marel, G A
Overkleeft, H S
van Boom, J H
Noort, D #
Issue Date: Jun-2003
Series Title: The journal of peptide research : official journal of the American Peptide Society vol:61 issue:6 pages:298-306
Abstract: As part of a program towards the development of novel antibiotics, a convenient method for solid-phase synthesis of the cyclic cationic peptide polymyxin B1 and analogues thereof is described. The methodology, based on cleavage-by-cyclization using Kenner's safety-catch linker, yields crude products with purities ranging from 37-67%. Antibacterial assays revealed that analogues 23-26, in which the (S)-6-methyloctanoic acid moiety is replaced with shorter acyl chains, exhibit distinct antimicrobial activity. The results suggest that the length of the acyl chain is rather critical for antimicrobial activity. On the other hand, substitution of the hydrophobic ring-segment D-Phe-6/Leu-7 in polymyxin B1 with dipeptide mimics (i.e. analogues 27-33) resulted in almost complete loss of antimicrobial activity.
ISSN: 1397-002X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Pharmaceutical Analysis
× corresponding author
# (joint) last author

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