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Modification of Peptides Using bis(thioether) ArylBridge (tABTM) Approach
Patent Number: US9556229B2
​
Executive Summary:
  • Invention Type: Therapeutic
  • Patent Status: Granted
  • Patent Link: https://patents.google.com/patent/US9556229B2
  • Related Patent Link: https://patents.google.com/patent/WO2017044592A1
  • Research Institute: University of California, Los Angeles
  • Disease Focus: Brain tumors
  • Basis of Invention: Holding proteins together with a molecular staple which constricts motion and prolongs life of protein by making breakdown by extracellular proteases more difficult
  • How it works: Stapling proteins together by strategically inserting cysteine residues within the target peptide sequence which facilitates the formation of a linker called bis(thioether)-Aryl-Bridge (tABM)
  • Lead Challenge Inventor: Piotr Ruchala
  • Inventors: Piotr Ruchala and Ewa Micewicz
  • Development Stage: Preclinical
  • Novelty:
    • Technology which allows for strategically placed cysteine residues to be linked together to extend the life of therapeutic proteins by constraining them into an alpha helical conformation.
  • Clinical Applications: Can be used to extend the life of promising drug-like proteins which have issues with being degraded rapidly while in circulation or during delivery to target tissues
 
General Description:
​
Apoptosis (programmed cell death) is coordinated and tightly regulated. This regulation is coordinated by Inhibitors of Apoptotic Proteins (IAPs), which are in turn regulated by SMACs (second mitochondria derived activator of caspases). SMACs belong to a family of proteins know as pro-apoptotics, which promote apoptosis. If cancer cells could specifically be selected for cell death, it could drive down toxicity and/or adverse effects from current therapies.
 
Scientific Progress:
Some of the tAB-developed peptides showed in vitro and in vivo bioactivity.
 
Future Directions:
  • Clinical validation
 
Strengths:
  • Applicability to glioblastoma and other cancers
 
Weaknesses:
  • Not yet tested in humans
 
Patent Status:
Legal status: Granted
  • Priority date: 2012-05-18
  • Filing date: 2013-05-17
  • Publication date: 2017-01-31
  • Grant date: 2017-01-31
 
Publication PMID: 24582479

Publication:
Micewicz ED, Luong HT, Jung CL, Waring AJ, McBride WH, Ruchala P. Novel dimeric Smac analogs as prospective anticancer agents. Bioorg Med Chem Lett. 2014 Mar 15;24(6):1452-7.
 
Inventor Bio: Piotr Ruchala
http://pet.ucla.edu/research_team_member/piotr-ruchala-ph-d-associate-project-scientist/
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