Potent CXCR4 antagonists containing amidine type Peptide bond isosteres.

Basic Information

ID: ALA2040720

Journal: ACS Med Chem Lett

Title: Potent CXCR4 antagonists containing amidine type Peptide bond isosteres.

Authors: Inokuchi E, Oishi S, Kubo T, Ohno H, Shimura K, Matsuoka M, Fujii N.

Abstract: A series of FC131 [cyclo(-d-Tyr-Arg-Arg-Nal-Gly-)] analogues containing amidine type peptide bond isosteres were synthesized as selective CXC chemokine receptor type 4 (CXCR4) antagonists. An isosteric amidine substructure was constructed by a macrocyclization process using nitrile oxide-mediated C-N bond formation. All of the amidine-containing FC131 analogues exhibited potent SDF-1 binding inhibition to CXCR4. The Nal-Gly-substituted analogue was characterized as one of the most potent cyclic pentapeptide-based CXCR4 antagonists reported to date. The improved activity against human immunodeficiency virus (HIV) type-1 X4 strains suggested that addition of another basic amidine group to the peptide backbone effectively increases the selective binding of the peptides to CXCR4 receptor.

CiteXplore: 24900333

DOI: 10.1021/ml200047e

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