Synthesis and biological evaluation of strained unusual amino acid containing tetrapeptides as potential antidepressant agents |
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| Institution: | 1. Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India;2. Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India;3. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Balanagar, Hyderabad 500037, India;1. Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA;2. Highly Pathogenic Viruses ZBS1, Centre for Biological Threats and Special Pathogens, Robert Koch Institute, Nordufer 20, 13353 Berlin, Germany;1. INRS – Institut Armand-Frappier, Groupe de Recherche en Ingénierie des Peptides et en Pharmacothérapie (GRIPP), Université du Québec, Ville de Laval, QC, Canada;2. INRS – Institut Armand-Frappier, Laboratoire d''études moléculaires et pharmacologiques des peptides (LEMPP), Université du Québec, Ville de Laval, QC, Canada;3. Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada;1. Department of Surgery, University of Michigan, Ann Arbor, MI;2. Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA;1. Department of Biochemistry and Applied Biosciences, University of Miyazaki, 1-1 Gakuenkibanadai-Nishi, Miyazaki 889-2192, Japan;2. Interdisciplinary Graduate School of Agriculture and Engineering, University of Miyazaki, 1-1 Gakuenkibanadai-Nishi, Miyazaki 889-2192, Japan;3. Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH 43614, USA;1. Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, United States;2. Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, United States;3. Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, United States |
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| Abstract: | Strained unusual amino acid derived tetrapeptides were synthesized as mimics of GLYX-13, a clinical candidate for neuroprotective and anti-depressant properties, were studied. The synthesized compounds were screened for neurite growth and anti-depressant properties in vitro and in vivo respectively comparing with the parent GLYX-13 compound. Neurite growth property was assessed by neurite length and anti-depressant property by percentage of immobility in forced swim test, a behavioural assay. Mechanistic insights about protein–ligand interactions were obtained using molecular docking study. Based on the in vitro and in vivo screening data and molecular docking study, a new analogue of GLYX-13, Compound 11a has been found to be as good as the parent compound in all respects. |
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| Keywords: | NMDA receptor GRIN2B Norbornane amino acid Neurotrophic |
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