Rigid Peptide Scaffold‐Incorporated Structural Analogs of the Potent Antidepressant Peptide Drug Rapastinel (GLYX‐13). Issue 12 (27th April 2017)

• Record Type: Journal Article
• Authors: Nadimpally, Krishna Chaitanya; Chakrapani, Aswathi; Prabhu, Priyanka J; Madica, Krishnaprasad; Sanjayan, Gangadhar J.
• Is Part Of: ChemistrySelect. Volume 2:Issue 12(2017)
• Page Start: 3594
• Page End: 3596
• Publication Date: 2017-04-27
• Subjects: β-amino acid -- Major depressive disorder -- Peptide drug -- Rapastinel; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.201700605
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: Abstract :Rapastinel (GLYX‐13) is a natural amidated tetrapeptide (Thr‐Pro‐Pro‐Thr‐NH2 )endowed with strong antidepressant property. Rapastinel shows considerable promise for treating drug‐resistant major depressive disorder (MDD), and is under clinical phase III development. Herein, we report the synthesis of a novel class of analogues of the potent antidepressant peptide drug rapastinel featuring rigid dipeptide scaffolds comprising proline (L/D) and amino thiophene carboxylates (Atc). Amino thiophene carboxylate is a conformationally constrained aromatic β‐amino acid, known to rigidify peptide backbones thereby limiting the conformational flexibility of peptides and improving proteolytic stability. Abstract : In this paper, we report the synthesis of a novel class of analogs of the potent antidepressant peptide drug rapastinel featuring rigid dipeptide scaffolds consisting of proline (L/D) and conformationally constrained β‐amino acid (amino thiophene carboxylates). *Peptide Drug, Major Depressive Disorder