Structure-activity relationships of the peptide deformylase inhibitor BB-3497: modification of the metal binding group

Helen K Smith; R Paul Beckett; John M Clements; Sheila Doel; Stephen P East; Steven B Launchbury; Lisa M Pratt; Zoë M Spavold; Wayne Thomas; Richard S Todd; Mark Whittaker

doi:10.1016/s0960-894x(02)00790-4

Structure-activity relationships of the peptide deformylase inhibitor BB-3497: modification of the metal binding group

Bioorg Med Chem Lett. 2002 Dec 16;12(24):3595-9. doi: 10.1016/s0960-894x(02)00790-4.

Authors

Helen K Smith¹, R Paul Beckett, John M Clements, Sheila Doel, Stephen P East, Steven B Launchbury, Lisa M Pratt, Zoë M Spavold, Wayne Thomas, Richard S Todd, Mark Whittaker

Affiliation

¹ British Biotech Pharmaceuticals Limited, Watlington Road, Oxford OX4 6LY, UK.

PMID: 12443784
DOI: 10.1016/s0960-894x(02)00790-4

Abstract

A series of analogues of the potent peptide deformylase (PDF) inhibitor BB-3497 containing alternative metal binding groups was synthesised. Enzyme inhibition and antibacterial activity data for these compounds revealed that the bidentate hydroxamic acid and N-formyl hydroxylamine structural motifs represent the optimum chelating groups on the pseudopeptidic BB-3497 backbone.

MeSH terms

Amidohydrolases*
Aminopeptidases / antagonists & inhibitors*
Bacteria / drug effects
Binding Sites
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / pharmacology
Escherichia coli Proteins / antagonists & inhibitors
Hydroxamic Acids / chemical synthesis*
Hydroxamic Acids / pharmacology*
Inhibitory Concentration 50
Metals / chemistry*
Microbial Sensitivity Tests
Structure-Activity Relationship

Substances

BB3497
Enzyme Inhibitors
Escherichia coli Proteins
Hydroxamic Acids
Metals
Aminopeptidases
Amidohydrolases
peptide deformylase