Singh Shalini, Shrivastava Richa, Singh Gajendra, Ali Rafat, Sankar Ampapathi Ravi, Bhadhuria Smrati, Haq Wahajul
Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India.
Toxicology Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India.
Chembiochem. 2017 Jun 19;18(12):1061-1065. doi: 10.1002/cbic.201700031. Epub 2017 May 11.
We report the synthesis and biological and physiochemical properties of a series of azaGly-appended peptidomimetics. We have developed a simple and facile synthesis for azapeptides on solid support without any side reaction. The azaGly is inserted by in situ reaction of disuccinimidyl carbonate with free amine followed by treatment of hydrazine hydrate at room temperature. The new series of peptidomimetics was prepared by azaGly scanning of heptapeptide Arg-Pro-Arg-Nle-Tyr-Dap-Nle (Akt-01), a GSK-3β-derived Akt inhibitor. The azaGly-appended peptides showed significant improvement in biological activity and serum stability, with retention of conformation as evidenced by NMR and CD studies. The results clearly demonstrate that azaGly-appended peptides are new peptidomimetics. Their synthesis makes this approach highly useful for the development of novel peptidomimetics of therapeutic potential.
