Cyclic aza-peptide integrin ligand synthesis and biological activity

Jochen Spiegel, Carlos Mas-Moruno, Horst Kessler, William D. Lubell

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Aza-peptides are obtained by replacement of the α-C-atom of one or more amino acids by a nitrogen atom in a peptide sequence. Introduction of aza-residues into peptide sequences may result in unique structural and pharmacological properties, such that aza-scanning may be used to probe structure-activity relationships. In this study, a general approach for the synthesis of cyclic aza-peptides was developed by modification of strategies for linear aza-peptide synthesis and applied in the preparation of cyclic aza-pentapeptides containing the RGD (Arg-Gly-Asp) sequence. Aza-amino acid scanning was performed on the cyclic RGD-peptide Cilengitide, cyclo[R-G-D-f-N(Me)V] 1, and its parent peptide cyclo(R-G-D-f-V) 2, potent antagonists of the αvβ3, αvβ5, and α5β1 integrin receptors, which play important roles in human tumor metastasis and tumor-induced angiogenesis. Although incorporation of the aza-residues resulted generally in a loss of binding affinity, cyclic aza-peptides containing aza-glycine retained nanomolar activity toward the αvβ3 receptor.

Original languageEnglish
Pages (from-to)5271-5278
Number of pages8
JournalJournal of Organic Chemistry
Volume77
Issue number12
DOIs
StatePublished - 15 Jun 2012

Fingerprint

Dive into the research topics of 'Cyclic aza-peptide integrin ligand synthesis and biological activity'. Together they form a unique fingerprint.

Cite this