title: RGD mimetics γ-AApeptides and methods of use (US 20,140,004,039 A1): a patent evaluation.
abstract: The patent (US 20140004039 A1) claims Arg-Gly-Asp (RGD) mimetics based on a new type of peptidomimetics - γ-AApeptides - which display high binding affinity and specificity to integrin αvβ3. Integrin αvβ3 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 αvβ3 is frequently upregulated during tumor angiogenesis, molecules mimicking the RGD recognition motif may target αvβ3 specifically and therefore can be used for cancer prevention or targeted diagnosis. Indeed, several positron emission tomography tracers targeting αvβ3 are currently under clinical investigation. γ-AApeptides as a new class of peptidomimetics show enhanced stability against proteolytic degradation and are amendable for derivatization due to their enormous chemodiversity. γ-AApeptide-based RGD mimetics, including linear, cyclic and multimeric γ-AApeptides, display comparable binding affinity and specificity to integrin αvβ3. 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 γ-AApeptide-based peptidomimetics are more stable than RGD peptides, they could be novel agents for the diagnostics and treatment of various cancers.
authors.affiliation: a Department of Pharmaceutical Chemistry , University of California , San Francisco, San Francisco , CA 94158 , USA.|b Department of Chemistry , University of South Florida , Tampa , FL 33620 , USA.
authors.forename: Haifan
authors.initials: H
authors.lastname: Wu
authors.affiliation: c College of Chemistry and Chemical Engineering , Central South University , Changsha , HN 410083 , P. R. China.
authors.forename: Jinzhi
authors.initials: J
authors.lastname: Jiang
authors.affiliation: c College of Chemistry and Chemical Engineering , Central South University , Changsha , HN 410083 , P. R. China.
authors.forename: Hai
authors.initials: H
authors.lastname: Xu
authors.affiliation: d Department of Medical Oncology, Shuguang Hospital , Shanghai University of Traditional Chinese Medicine , Shanghai 201203 , China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: b Department of Chemistry , University of South Florida , Tampa , FL 33620 , USA.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Cai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D051379:Mice; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010330:Patents as Topic; D049268:Positron-Emission Tomography
chemical_list: D000970:Antineoplastic Agents; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid
keywords: PET imaging; RGD peptide; angiogenesis; integrin αvβ3; γ-AApeptide