title: AzaGly-Appended Peptidomimetics Structurally Related to PTR6154 as Potential PKB/Akt Inhibitors.
abstract: 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.
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India.
authors.forename: Shalini
authors.initials: S
authors.lastname: Singh
authors.affiliation: Toxicology Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India.|Academy of Scientific and Innovative Research, New Delhi, 11000, India.
authors.forename: Richa
authors.initials: R
authors.lastname: Shrivastava
authors.affiliation: NMR Centre, SAIF, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India.|Academy of Scientific and Innovative Research, New Delhi, 11000, India.
authors.forename: Gajendra
authors.initials: G
authors.lastname: Singh
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India.
authors.forename: Rafat
authors.initials: R
authors.lastname: Ali
authors.affiliation: NMR Centre, SAIF, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India.|Academy of Scientific and Innovative Research, New Delhi, 11000, India.
authors.forename: Ravi
authors.initials: R
authors.lastname: Sankar Ampapathi
authors.affiliation: Toxicology Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India.|Academy of Scientific and Innovative Research, New Delhi, 11000, India.
authors.forename: Smrati
authors.initials: S
authors.lastname: Bhadhuria
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India.|Academy of Scientific and Innovative Research, New Delhi, 11000, India.
authors.forename: Wahajul
authors.initials: W
authors.lastname: Haq
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001372:Aza Compounds / Q000737:chemistry*; D045744:Cell Line, Tumor; D015195:Drug Design; D004355:Drug Stability; D015972:Gene Expression Regulation, Neoplastic; D000071679:Glycogen Synthase Kinase 3 beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006834:Hydrazines / Q000737:chemistry; D062105:Molecular Docking Simulation; D009842:Oligopeptides / Q000737:chemistry*; D057786:Peptidomimetics / Q000138:chemical synthesis* / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D017433:Protein Structure, Secondary; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D060327:Solid-Phase Synthesis Techniques / Q000379:methods; D013388:Succinimides / Q000737:chemistry; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D001372:Aza Compounds; C550755:H-Arg-Pro-Arg-Nva-Tyr-Dap-Hol-NH2; D006834:Hydrazines; D009842:Oligopeptides; D057786:Peptidomimetics; D013388:Succinimides; C029424:hydrazine; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt inhibitors; azaglycine; azo compounds; peptidomimetics; solid phase peptide synthesis