The patent (US 20140004039 A1) claims Arg-Gly-Asp (RGD) mimetics based on a new type of peptidomimetics -gamma-AApeptides - which display high binding affinity and specificity to integrin alpha(v)beta(3). Integrin alpha(v)beta(3) is one of the most important proteins involved in tumor angiogenesis and metastasis of solid tumors. It binds tightly to the tripeptide RGD, a prominent recognition motif found in extracellular matrix proteins. As alpha(v)beta(3) is frequently upregulated during tumor angiogenesis, molecules mimicking the RGD recognition motif may target alpha(v)beta(3) specifically and therefore can be used for cancer prevention or targeted diagnosis. Indeed, several positron emission tomography tracers targeting alpha(v)beta(3) are currently under clinical investigation gamma-AApeptides as a new class of peptidomimetics show enhanced stability against proteolytic degradation and are amendable for derivatization due to their enormous chemodiversity gamma-AApeptide-based RGD mimetics, including linear, cyclic and multimeric gamma-AApeptides, display comparable binding affinity and specificity to integrin alpha(v)beta(3). These RGD mimetics can be synthesized easily on the solid phase and have been shown to be excellent positron emission tomography tracers by targeting glioblastoma tumor on the mouse model. As -AApeptide-based peptidomimetics are more stable than RGD peptides, they could be novel agents for the diagnostics and treatment of various cancers.
[1]Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.
[2]Univ S Florida, Dept Chem, Tampa, FL 33620 USA.
[3]Cent South Univ, Coll Chem & Chem Engn, Changsha 410083, Hunan, Peoples R China.
[4]Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Dept Med Oncol, Shanghai 201203, Peoples R China.
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