108456-08-2Relevant academic research and scientific papers
Use of Molecular Modeling to Design Selective NTS2 Neurotensin Analogues
Fanelli, Roberto,Floquet, Nicolas,Besserer-Offroy, élie,Delort, Bartholomé,Vivancos, Mélanie,Longpré, Jean-Michel,Renault, Pedro,Martinez, Jean,Sarret, Philippe,Cavelier, Florine
, p. 3303 - 3313 (2017)
Neurotensin exerts potent analgesia by acting at both NTS1 and NTS2 receptors, whereas NTS1 activation also results in other physiological effects such as hypotension and hypothermia. Here, we used molecular modeling approach to design highly selective NT
Stereoselective Synthesis of β-(5-Arylthiazolyl) α-Amino Acids and Use in Neurotensin Analogues
Hap?u, Denisa,Rémond, Emmanuelle,Fanelli, Roberto,Vivancos, Mélanie,René, Adeline,C?té, Jér?me,Besserer-Offroy, élie,Longpré, Jean-Michel,Martinez, Jean,Zaharia, Valentin,Sarret, Philippe,Cavelier, Florine
, p. 1017 - 1024 (2016/03/01)
A series of new unnatural amino acids bearing a β-arylthiazole side chain was synthesized by exploiting a diastereoselective alkylation starting from glycine tert-butyl ester Schiff base with hydroxypinanone as the chiral inducer. This strategy afforded β-arylthiazole alanines in good chemical yields and with 98 % ee. Due to their aromatic properties, these newly generated amino acids were used to prepare neurotensin (NT)[8-13] analogues by serving as replacements for the native Tyr11 residue. Incorporation of the (L)-(+)-(β-phenylthiazol-4-yl)alanine residue at NT[8-13] position 11 improved plasma stability and selectivity towards NTS1, while also preserving native receptor binding affinity and biological activity. New β-arylthiazole alanines were synthesized in good chemical yields and with 98 % ee using a diastereoselective alkylation; these alanine derivatives were then used as Tyr11 replacements in the construction of neurotensin (NT)[8-13] analogues. The new NT analogues showed improved plasma stability and selectivity towards NTS1 thus preserving the hypotensive properties of the native peptide.
Synthesis of new substance P analogues releasing histamine from rat peritoneal mast cells
Chen,Mousli,Thoret,Fischer,Landry,Michelot
, p. 931 - 937 (2007/10/02)
New analogues of the N-terminal fragment of substance P [Arg-Pro-Lys-Pro, SP(1-4)] were synthesized and their activities on histamine release from rat peritoneal mast cells were compared. The potency of these compounds decreases in the following order (in abbreviation): SP(1-4)C12 > C'12-SP(1-4)-OCH3 > C'12-SP(1-4)-OH, H-Lys-Pro-C12 and SP. Benzalkonium chloride, a competitive antagonist of peptide-induced histamine release from rat mast cells, inhibits the effect of SP and SP analogues with IC50 in the range of micromolar concentrations. SP(1-4)-C12 and C'12-SP(1-4)-OCH3 have been found to be 10-fold more active than SP on the GTPase activity of purified G proteins (G(o)/G(i)). The lack of clear structural relationships for agonist activities supports a receptor-less mechanism for histamine release by SP and its analogs. This effect could be elicited by a direct stimulation of G proteins.
