Craig Townsend

Abstract Nonribosomal peptide synthetases (NRPSs) underlie the biosynthesis of many natural products that have important medicinal utility. Protection of the NRPS peptide products from proteolysis is critical to these pathways and is often achieved by structural modification, principally the introduction of d-amino acid residues into the elongating peptide.

Highlights • Facile synthesis of structurally complex, reactive peptide methylfluorophosphonates • Diverse functional group tolerance without protecting groups • Mechanistic studies support the intermediacy of a difluorophosphonate • Specific inactivation of the nocardicin biosynthetic thioesterase exemplified Summary Diphenylphosphonates (DPPs) have been used for 50 years to inactivate serine hydrolases, creating adducts representative of tetrahedral intermediates of this important class of...

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