Document Report Card

Basic Information

ID: ALA1806363

Journal: Bioorg Med Chem Lett

Title: New substrate analogue furin inhibitors derived from 4-amidinobenzylamide.

Authors: Becker GL, Hardes K, Steinmetzer T.

Abstract: A series of new peptidomimetic furin inhibitors was synthesized, which was derived from our previously described lead structure phenylacetyl-Arg-Val-Arg-4-amidinobenzylamide (1). Substitution of Val by other amino acid residues revealed several highly potent furin inhibitors with K(i) values of less than 2nM, containing guanidinoalanine, Ile, Phe or Tyr in the P3 position. The replacement of the P2 Arg by Lys was also well accepted, whereas the incorporation of D-amino acids at various positions resulted in poor inhibitors. The use of the 4-amidinobenzylamide group provides convenient synthetic access to stable proprotein convertase inhibitors and derivatives as biochemical tools and for further studies in cell culture.

CiteXplore: 21757345

DOI: 10.1016/j.bmcl.2011.06.091