The Constrained Amino Acid β-Acc Confers Potency and Selectivity to Integrin Ligands

✍ Scribed by Sylwia Urman; Katharina Gaus; Yi Yang; Ulf Strijowski; Norbert Sewald; Silvia De Pol; Oliver Reiser

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 181 KB
• Volume: 46
• Category: Article
• ISSN: 0044-8249
• DOI: 10.1002/anie.200605248

✦ Synopsis

Interactions between the extracellular matrix and membrane proteins are of importance for cell adhesion, tissue formation, and transmembrane signaling processes. Among cell adhesion molecules, integrins occupy a highly prominent position. Many integrins, among them a 5 b 1 and a V b 3 , recognize the tripeptide sequence -Arg-Gly-Asp-(RGD) in their ligands. The discovery of the role of the RGD sequence in cell-cell and cell-matrix interactions prompted the development of a broad variety of RGD peptides and peptidomimetics for potential therapeutic applications. Soluble derivatives of these compounds are able to competitively inhibit the interaction between an RGD-containing protein and its integrin counterpart, whereas immobilized RGD peptides support cell attachment, for example, to artificial implants. [1] Integrins play a crucial role in numerous disorders. Integrin a v b 3 promotes angiogenesis, which is an essential event in proliferation and metastatis of human tumors, regulates adhesion of cancer cells, and participates in the progression of osteoporosis. [2] Although integrin a 5 b 1 is also involved in angiogenesis, it participates predominantly in various inflammatory disorders, for example, asthma and rheumatoid arthritis. [3] Therefore, the discovery of new peptide ligands displaying high activity and selectivity is a challenge for both biochemistry and medicinal chemistry.

The rational design of biologically active peptides involves prediction of their three-dimensional structure. Spatial screening of peptides and peptidomimetics is an