Biological Data and Docking Experiments of bFGF-Sulfonated Distamycin a Derivative Complex
A series of sulfonated derivatives of Distamycin A have been synthesized with the objective of identifying novel compounds able to complex bFGF, which is involved in tumor angiogenesis, and consequently to block the angiogenic process.
These new compounds have been characterized for their ability of inhibiting bFGF binding, in vivo bFGF iSnduced angiogenesis and neovascularization of the chorioallantoic membrane and antitumor activity on M5076 murine reticulosarcoma.
A set of molecules was docked to the known three-dimensional structure of the growth factor and a possible feature of the bFGF-ligand complex was deduced.
Sulfonated Distamycin A derivatives act as bidental ligands interacting with both the heparin and receptor binding sites of bFGF in a 1:1 ratio. The consistency of computational and biological results supports this approach for explaning the interaction between bFGF and sulfonated Distamycin A derivatives.
KeywordsSulfonate Group Receptor Binding Site Chorioallantoic Membrane Solid Tumor Growth Heparin Binding Site
Unable to display preview. Download preview PDF.
- 1.D. Benharroch and D. Birnhaum, Irs.J.Med.Sci. 26, 212 (1990).Google Scholar
- 4.N. Mongelli et al., U.K. Patent n. 91902204. 6 (1991).Google Scholar
- 5.M. Ciomei et al., in preparation.Google Scholar
- 6.K. Steliou, Program MODEL (Version KS 2.99) and BAKMDL, University of Montreal, Canada.Google Scholar
- 7.W.C. Still, Program MacroModel (Version 3.0) and BatchMin (Version 3.1), Department of Chemistry, Columbia University, New York, N.Y., USA.Google Scholar
- 8.MOPAC (Molecular orbita package), QCPE Creative Arts Bldg. 181, Indiana University, Bloomington, IN, USA.Google Scholar
- 9.Sybyl, Tripos Assiactes, St. Louis, MO, USA.Google Scholar
- 10.A full account on the chemistry of FCE compounds will be reported elesewhere.Google Scholar