Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Curr Pharm Des. 2006;12(22):2749-69.

Integrins in drug targeting-RGD templates in toxins.

Author information

  • 1Thrombosis Research Institute, Manresa Road, London, SW3 6LR UK. xlu@tri-london.ac.uk

Abstract

Integrins are a family of heterodimeric receptors, which modulate many cellular processes including: growth, death (apoptosis), adhesion, migration, and invasion by activating several signaling pathways. Integrin-binding RGD (arginine-glycine-aspartic acid) is found in several important extracellular matrix proteins which serve as adhesive integrin ligands. The RGD motif has also been found in many toxins from snake venom and other sources that specifically inhibit integrin binding function and serve as potent integrin antagonists, particularly of platelet aggregation and integrin-mediated cell adhesion. Many of these proteins have potential as therapeutic agents which can target integrins directly. Structural and functional studies of several RGD-containing toxins suggest that the inhibitory potency of these proteins lies in subtle positional requirements of the tripeptide RGD at the tip of a flexible loop, a structural feature for binding to integrins. In addition, amino acid residues in this loop in close vicinity to the RGD-motif determine the integrin-binding specificity and selectivity. This review will present a review of integrin structure and function, and of disintegrin structural features responsible for their activity as antagonists of integrin function. The use of integrins in drug targeting and integrins as targets for drug delivery by using the RGD as a template structure will also be discussed.

PMID:
16918409
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Bentham Science Publishers Ltd.
    Loading ...
    Write to the Help Desk