During evolution, nature has developed avid and selective agonists and antagonists of integrin-mediated cell functions. Venoms are natural libraries of pharmacologically effective integrin inhibitors which are screened against the soluble integrin in a cell-free assay by the Eble lab. Thus, several RGD-independent inhibitors of collagen- and laminin-binding integrins have been identified and characterized (Bergmeier W, et al. 2001; Eble JA, et al. 2001; Zigrino P et al. 2002, Bolás, 2014 #120; Eble JA, et al. 2003; Eble JA and Tuckwell DS 2003; Brown MC et al. 2009; Eble JA et al. 2009; Juárez P et al. 2010; Sanchez EF, et al. 2010; Momic T, et al. 2011; Arlinghaus FT and Eble JA 2012; Momic T, et al. 2012; Arlinghaus FT and Eble JA 2013; Arlinghaus FT, et al. 2013). In addition, other snake venom components could be ruled out to interact with integrins. Among them, rhodocytin does not target 21 integrin, but the newly identified receptor CLEC2, thus resulting in platelet activation (Suzuki-Inoue K et al. 2006; Fuller GLJ et al. 2007; Watson A et al. 2007; Hughes CE et al. 2008; Mori J et al. 2008; Watson AA et al. 2008; Kerrigan AM et al. 2009; May F et al. 2009; Spalton JC et al. 2009; Hughes CE et al. 2010; Pollitt AY et al. 2010). Other snake venom components are biochemically analyzed in cooperation with Brazilian snake farms and additional research facilities in Spain and Israel (Sanchez EF et al. 2007; Sanchez EF and Eble JA 2009; Sanchez EF, et al. 2010; Tanjoni I, et al. 2010, Bolás, 2014 #120; Momic T, et al. 2011; Momic T, et al. 2012; Sanz-Soler R, et al. 2012; Cecilio AB et al. 2013; Jacubowski P, et al. 2013; Vivas-Ruiz DE, et al. 2013).
The (patho)physiological functions of the integrin inhibitors are analyzed in various cellular and physiological system, among them models of tumor progression and thrombosis (Eble JA 2005; Eble JA and Haier J 2006; Suzuki-Inoue K, et al. 2006; Fuller GLJ, et al. 2007; Hughes CE, et al. 2008; Rosenow F et al. 2008; Kerrigan AM, et al. 2009; Krähling H et al. 2009; Kusuma N, et al. 2012; Parguina AF, et al. 2012; De Cuyper IM, et al. 2013; Vivas-Ruiz DE, et al. 2013).
In parallel to their functions, the molecular structures of the integrin inhibitors are studied. The crystal structure, e.g. of the 21 integrin antagonist rhodocetin, provide insights into the molecular mechanism of integrin blockage and reveal potential lead structures to develop integrin-targeting pharmaceuticals (Watson AA, et al. 2008; Eble JA, et al. 2009; Bracht T et al. 2011).
The Eble lab appreciates the lively cooperations with various snake farms and venom research facilities in Brazil and Israel.
In addition to integrin inhibitors, snake venoms are a rich source for highly effective compounds interfering with a whole spectrum of physiological reactions, such as coagulation, thrombosis, regulation of cardiovascular integrity and function, of neuronal and muscular functions. As such, we could identify neuropilin-1 on endothelial cells as novel receptor for the subunit of rhodocetin leading to restructuring of the integrin-containing adhesome and stress fibers in endothelial cells (Niland S et al. 2013). But also CLEC-2 and GPIb were identified as potential target of C-type lectin-related proteins from snake venoms (Suzuki-Inoue K, et al. 2006; Fuller GLJ, et al. 2007; Watson A, et al. 2007; Kerrigan AM, et al. 2009; May F, et al. 2009; Hughes CE, et al. 2010; Pollitt AY, et al. 2010; Navdaev A et al. 2011; Séverin S et al. 2011; Parguina AF, et al. 2012; De Cuyper IM, et al. 2013).
The (patho)physiological functions of the integrin inhibitors are analyzed in various cellular and physiological system, among them models of tumor progression and thrombosis (Eble JA 2005; Eble JA and Haier J 2006; Suzuki-Inoue K, et al. 2006; Fuller GLJ, et al. 2007; Hughes CE, et al. 2008; Rosenow F et al. 2008; Kerrigan AM, et al. 2009; Krähling H et al. 2009; Kusuma N, et al. 2012; Parguina AF, et al. 2012; De Cuyper IM, et al. 2013; Vivas-Ruiz DE, et al. 2013).
In parallel to their functions, the molecular structures of the integrin inhibitors are studied. The crystal structure, e.g. of the 21 integrin antagonist rhodocetin, provide insights into the molecular mechanism of integrin blockage and reveal potential lead structures to develop integrin-targeting pharmaceuticals (Watson AA, et al. 2008; Eble JA, et al. 2009; Bracht T et al. 2011).
The Eble lab appreciates the lively cooperations with various snake farms and venom research facilities in Brazil and Israel.
In addition to integrin inhibitors, snake venoms are a rich source for highly effective compounds interfering with a whole spectrum of physiological reactions, such as coagulation, thrombosis, regulation of cardiovascular integrity and function, of neuronal and muscular functions. As such, we could identify neuropilin-1 on endothelial cells as novel receptor for the subunit of rhodocetin leading to restructuring of the integrin-containing adhesome and stress fibers in endothelial cells (Niland S et al. 2013). But also CLEC-2 and GPIb were identified as potential target of C-type lectin-related proteins from snake venoms (Suzuki-Inoue K, et al. 2006; Fuller GLJ, et al. 2007; Watson A, et al. 2007; Kerrigan AM, et al. 2009; May F, et al. 2009; Hughes CE, et al. 2010; Pollitt AY, et al. 2010; Navdaev A et al. 2011; Séverin S et al. 2011; Parguina AF, et al. 2012; De Cuyper IM, et al. 2013).