TY - JOUR
T1 - Interaction between basic fibroblast growth factor and the anti-angiogenic drug PNU145156E
AU - Zamai, Moreno
AU - Hariharan, Chithra
AU - Pines, Dina
AU - Safran, Michal
AU - Yayon, Avner
AU - Caiolfa, Valeria R.
AU - Mariani, Mariangela
AU - Pines, Ehud
AU - Cohen-Luria, Rivka
AU - Parola, Abraham H.
N1 - Funding Information:
We are most grateful for the technical help to Batia Uzan and I. Fishov (Ben-Gurion University, Israel). We thank F. Kezdy (Pharmacia Corp. Kalamazoo), D. Gill (Ben-Gurion University, Israel), and M. Grandi for their suggestions and critical review, G. Bolis and A. Vulpetti (Nerviano Medical Sciences, Italy) for discussing X-ray and modeling data, and D.E. Epps and R.W. Sarver (Pharmacia Corp. Kalamazoo, USA). We thank the Israel Science Foundation, for the purchase of the K-2 Multifrequency phase-modulation spectrofluorometer. This work was partially supported by the Vice-President of Research and Development, Ben-Gurion University of the Negev, the ONR, the Israel Science Foundation, the James Franck Center for Laser-Matter Interaction and by the “Ministero per l’Istruzione e la Ricerca Scientifica” (MIUR), Italy.
PY - 2006/7/3
Y1 - 2006/7/3
N2 - Solid tumors require the formation of a vascular network derived from host blood vessels to support their growth. The heparin-binding growth factor family was the first class of angiogenesis factors to be studied. These proteins play key roles in a variety of crucial biological activities that require cell growth, differentiation, migration and chemotaxis. Our work presents the study of a group of polyanionic compounds, the naphthalene sulfonic distamycin A derivatives, named suradistas, which represents a new class of inhibitors of neo-angiogenesis that can counteract vascularization of solid tumors. By a combination of in vitro and in vivo approaches, a leader compound, PNU145156E, was selected. The results suggest that PNU145156E interacts directly with the heparin-binding growth factor bFGF in a specific manner. It forms a tight but reversible 1 to 1 complex with the protein, inducing conformational changes, which render bFGF less stable, preventing the interaction with heparin and the biologically effective dimerization of the growth factor.
AB - Solid tumors require the formation of a vascular network derived from host blood vessels to support their growth. The heparin-binding growth factor family was the first class of angiogenesis factors to be studied. These proteins play key roles in a variety of crucial biological activities that require cell growth, differentiation, migration and chemotaxis. Our work presents the study of a group of polyanionic compounds, the naphthalene sulfonic distamycin A derivatives, named suradistas, which represents a new class of inhibitors of neo-angiogenesis that can counteract vascularization of solid tumors. By a combination of in vitro and in vivo approaches, a leader compound, PNU145156E, was selected. The results suggest that PNU145156E interacts directly with the heparin-binding growth factor bFGF in a specific manner. It forms a tight but reversible 1 to 1 complex with the protein, inducing conformational changes, which render bFGF less stable, preventing the interaction with heparin and the biologically effective dimerization of the growth factor.
KW - Angiogenesis
KW - Cancer
KW - Fluorescence spectroscopy
KW - Heparin-binding growth factors
KW - Naphthalene sulfonic distamycin A derivatives
KW - Suradista
KW - bFGF
UR - https://www.scopus.com/pages/publications/33745671298
U2 - 10.1016/j.molstruc.2006.03.062
DO - 10.1016/j.molstruc.2006.03.062
M3 - Article
AN - SCOPUS:33745671298
SN - 0022-2860
VL - 792-793
SP - 23
EP - 35
JO - Journal of Molecular Structure
JF - Journal of Molecular Structure
ER -
