01260nas a2200157   4500008004100000245012400041210006900165260000800234300001400242490000700256520062200263100002600885700003500911700002800946856012800974       2017                        eng d00aNovel silaproline (Sip)-incorporated close structural mimics of potent antidepressant peptide drug rapastinel (GLYX-13)0 aNovel silaproline Sipincorporated close structural mimics of pot  cAPR  a1568-15710 v583 aRapastinel (GLYX-13) is a C-amidated tetrapeptide drug under clinical development for adjunctive treatment of major depressive disorder (MDD). Rapastinel features two consecutive proline residues centered at the peptide sequence (Thr-Pro-Pro-Thr-NH2), which are detrimental to its biological activity. In this communication, we report the synthesis of very close structural analogues of rapastinel comprising silaproline (Sip) as proline surrogate. By virtue of its enhanced lipophilicity and metabolic stability, Sip introduction in the native rapastinel sequence is expected to improve its pharmacokinetic profiles.1 aMadica, Krishnaprasad1 aNadimpally, Krishna, Chaitanya1 aSanjayan, Gangadhar, J.  uhttps://library.ncl.res.in/content/novel-silaproline-sip-incorporated-close-structural-mimics-potent-antidepressant-peptide01423nas a2200181   4500008004100000245012200041210006900163260000800232300001400240490000600254520071400260100003500974700002401009700002501033700002601058700002801084856012901112       2017                        eng d00aRigid peptide scaffold-incorporated structural analogs of the potent antidepressant peptide drug rapastinel (GLYX-13)0 aRigid peptide scaffoldincorporated structural analogs of the pot  cAPR  a3594-35960 v23 a<p>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 beta-amino acid, known to rigidify peptide backbones thereby limiting the conformational flexibility of peptides and improving proteolytic stability.</p>1 aNadimpally, Krishna, Chaitanya1 aChakrapani, Aswathi1 aPrabhu, Priyanka, J.1 aMadica, Krishnaprasad1 aSanjayan, Gangadhar, J.  uhttps://library.ncl.res.in/content/rigid-peptide-scaffold-incorporated-structural-analogs-potent-antidepressant-peptide-drug01636nas a2200277   4500008004100000022001400041245009300055210006900148260000900217300001600226490000600242520073400248653001300982653001200995653002101007653001301028653001301041100002601054700003001080700001801110700003501128700002001163700002401183700002801207856012301235       2019                        eng d  a2365-654900aDimedone-based rigid organic scaffold for organizing symmetrical helical peptide chains.0 aDimedonebased rigid organic scaffold for organizing symmetrical   cOCT   a11518-115220 v43 a<p>We describe herein design, synthesis and conformational investigations of polypeptides attached on a rigid dimedone template. Two identical peptide chains are attached on a single carbon containing dimedone as a scaffold. Dimedone assists in controlling the secondary interactions through strong intramolecular helical C-12 and C-15 membered bifurcated hydrogen bonding on both the peptide chains along with propagating the helical architecture of the peptide chains attached. There exists a C-6 hydrogen bonding for the single stranded peptides attached to dimedone. Extensive structural investigations involving single crystal X-ray diffraction, solution-state NMR and CD studies of oligopeptides have been undertaken.</p>
10adimedone10aHelical10ahydrogen bonding10aPeptides10atemplate1 aMadica, Krishnaprasad1 aLakshmi, Jerripothula, K.1 aMadhu, Suresh1 aNadimpally, Krishna, Chaitanya1 aGonnade, Rajesh1 aJagadeesh, Bharatam1 aSanjayan, Gangadhar, J.  uhttps://library.ncl.res.in/content/dimedone-based-rigid-organic-scaffold-organizing-symmetrical-helical-peptide-chains