Structural Basis for Antagonism by Suramin of Heparin Binding to Vaccinia Complement Protein^,

Abstract

Suramin is a competitive inhibitor of heparin binding to many proteins, including viral envelope proteins, protein tyrosine phosphatases, and fibroblast growth factors (FGFs). It has been clinically evaluated as a potential therapeutic in treatment of cancers caused by unregulated angiogenesis, triggered by FGFs. Although it has shown clinical promise in treatment of several cancers, suramin has many undesirable side effects. There is currently no experimental structure that reveals the molecular interactions responsible for suramin inhibition of heparin binding, which could be of potential use in structure-assisted design of improved analogues of suramin. We report the structure of suramin, in complex with the heparin-binding site of vaccinia virus complement control protein (VCP), which interacts with heparin in a geometrically similar manner to many FGFs. The larger than anticipated flexibility of suramin manifested in this structure, and other details of VCP-suramin interactions, might provide useful structural information for interpreting interactions of suramin with many proteins.

Mo polyoxometalate nanoparticles inhibit tumor growth and vascular endothelial growth factor induced angiogenesis

“…We examined the effect of complexes 1 , 2 , and 3 with or without VEGF on the HUVECs’ migration, as measured by the wound healing assay. Suramin exhibits its antitumor activity in various cell lines [30, 31], which has been clinically evaluated as a potential therapeutic in treatment of cancers caused by VEGF-induced angiogenesis; therefore, we have chosen it as a positive control. Figure 5(a) showed that for VEGF-induced angiogenesis, VEGF facilitated repair of the wounded monolayer by 24 h, and a significant area of the wound remained uncovered when treated with complexes 1 , 2 , and 3 compared to the control.…”

Adeno-Associated Viral Vectors Based on Serotype 3b Use Components of the Fibroblast Growth Factor Receptor Signaling Complex for Efficient Transduction

“…When infection was performed in 2% serum with the addition of suramin (Fig. 3B), a molecule that binds and inhibits the activity of many of the heparinbinding growth factors (Moscatelli and Quarto, 1989;Ganesh et al, 2005), the heparin enhancement was abrogated, reinforcing the need for the presence of growth factors to achieve the heparin augmentation effect.…”

“…Low to moderate levels of GF (which may more closely reflect an in vivo scenario) are essential, not detrimental, to the enhancement. Removing them from the infection either through performing the infections under serum-free conditions, or by using suramin (a drug that blocks the biological activity of heparin-binding growth factors) (Moscatelli and Quarto, 1989;Ganesh et al, 2005), abolishes the affect. Addition of the growth factor back to the cells reconstitutes this effect.…”

Coordination phenomena of alkali metal, alkaline earth metal, and indium ions with the 1,3,6-naphthalenetrisulfonate ion in protic and aprotic solvents

“…Previously [7,16], the specific complexing behavior of alkali metal or alkaline earth metal ions with p-toluenesulfonate and 1,5-naphthalenedisulfonate ions has been thoroughly investigated in MeCN, alcohols, and binary solvents of MeCN-H 2 O and MeCN-alcohols. Naphthalenetrisulfonate is commonly used as a chemical function of Suramin and Suradistas [28].…”