RGD mimetics γ-AApeptides and methods of use (US 20,140,004,039 A1): a patent evaluation

Expert Opin Ther Pat. 2016;26(1):131-7. doi: 10.1517/13543776.2016.1111337. Epub 2015 Nov 11.


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.

Keywords: PET imaging; RGD peptide; angiogenesis; integrin αvβ3; γ-AApeptide.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Drug Design
  • Humans
  • Integrin alphaVbeta3 / metabolism*
  • Mice
  • Neoplasm Metastasis
  • Neoplasms / diagnosis
  • Neoplasms / drug therapy*
  • Neoplasms / prevention & control
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / pathology
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology*
  • Patents as Topic
  • Positron-Emission Tomography


  • Antineoplastic Agents
  • Integrin alphaVbeta3
  • Oligopeptides
  • arginyl-glycyl-aspartic acid