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Issue 21, 2015
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Synthesis of nisin AB dicarba analogs using ring-closing metathesis: influence of sp3versus sp2 hybridization of the α-carbon atom of residues dehydrobutyrine-2 and dehydroalanine-5 on the lipid II binding affinity

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Abstract

Herein the synthesis of two nisin AB dicarba analogs is described, focusing on amino acid modifications at positions 2 and 5. The nisin mimics were synthesized by a combination of solid phase synthesis of the linear peptides, followed by macrocyclization via ring-closing metathesis and fragment assembly by means of solution phase chemistry. The two N-terminal nisin AB-fragment mimics contain either the native dehydrobutyrine (Dhb)/dehydroalanine (Dha) amino acid residues or alanine at position 2 and 5, respectively. The native dehydrobutyrine at position 2 and dehydroalanine at position 5 were introduced as their precursors, namely threonine and serine, respectively, and subsequent dehydration was carried out by EDCI/CuCl as the condensing agent. Both AB-fragment mimics were analyzed in a lipid II binding assay and it was found that the Ala2/Ala5 AB-mimic (2) showed a reduced activity, while the Dhb2/Dha5 AB-mimic (3) was as active as the native AB-fragment (1).

Graphical abstract: Synthesis of nisin AB dicarba analogs using ring-closing metathesis: influence of sp3versus sp2 hybridization of the α-carbon atom of residues dehydrobutyrine-2 and dehydroalanine-5 on the lipid II binding affinity

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Publication details

The article was received on 18 Feb 2015, accepted on 27 Apr 2015 and first published on 28 Apr 2015


Article type: Paper
DOI: 10.1039/C5OB00336A
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Citation: Org. Biomol. Chem., 2015,13, 5997-6009
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    Synthesis of nisin AB dicarba analogs using ring-closing metathesis: influence of sp3versus sp2 hybridization of the α-carbon atom of residues dehydrobutyrine-2 and dehydroalanine-5 on the lipid II binding affinity

    J. C. Slootweg, Eric. F. van Herwerden, Mark. F. M. van Doremalen, E. Breukink, R. M. J. Liskamp and D. T. S. Rijkers, Org. Biomol. Chem., 2015, 13, 5997
    DOI: 10.1039/C5OB00336A

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