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Updated: Jun 1, 2026

A Fluorescence-based Protocol for Preliminary Screening of Protein Synthesis Inhibitors from Natural Sources
Published on: January 27, 2026
Design, synthesis and biological activity of novel peptidyl benzyl ketone FVIIa inhibitors
Morten Storgaard1, Signe T Henriksen, Florencio Zaragoza
1Technical University of Denmark, Department of Chemistry, Kemitorvet, Building 201, DK-2800 Kgs. Lyngby, Denmark.
Abstract:
Herein is described the synthesis of a novel class of peptidyl FVIIa inhibitors having a C-terminal benzyl ketone group. This class is designed to be potentially suitable as stabilization agents of liquid formulations of rFVIIa, which is a serine protease used for the treatment of hemophilia A and B inhibitor patients. A library of compounds was synthesized with different tripeptide sequences, N-terminals and d-amino acids in the P3 position. Cbz-D-Phe-Phe-Arg-bk (33) was found to be the best candidate with a potency of K(i)=8μM and no substantial inhibition of related blood coagulation factors (thrombin and FXa). Computational studies revealed that 33 has a very stable binding conformation due to intramolecular hydrogen bonds, which cannot be formed with l-Phe in the P3 position. Nonpolar amino acids were found to be superior, probably due to a minimization of the cost of desolvation upon binding to FVIIa.
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