Abstract
459 The FGF-2 binding domain of thrombospondin-1: functional characterization and exploitation to design antiangiogenic compounds
Highlights
Angiogenesis has become a successful target in cancer therapy [1]
Using recombinant portions of TSP-1, we identified a previously undescribed antiangiogenic site in the type III repeats of TSP-1, and demonstrated that binding of the angiogenic factor fibroblast growth factor (FGF)-2 to this site inhibits angiogenesis by sequestration of fibroblast growth factor-2 (FGF2) [31]
It is conceivable that TSP-1, its active sequence DD15 and the identified small molecule sm27 would bind and inhibit the activity of other angiogenic factors
Summary
Angiogenesis has become a successful target in cancer therapy [1]. Designed to target the formation of a functional vascular network – a requirement for the malignant progression -, antiangiogenic agents impair tumor growth and metastatic dissemination [2]. In particular the recent development of new exchange-based methods makes NMR spectroscopy a unique tool for accessing huge and heterogeneous systems reducing or eliminating the molecular weight limitations for receptors in interaction studies These methods, giving exchangetransferred structural information at high sensitivity on receptor-bound ligands from unbound-state resonances, are very useful to study the interactions of small molecules or proteins with very large systems, with no need of labeling [65,66,67]. Overall, these concepts provide a solid basis to integrate structural, dynamic, biochemical and molecular biology information explicitly in the drug discovery process. The molecular information on Endogenous inhibitor (TSP-1)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have