Fanelli, Roberto Besserer-Offroy, Élie René, Adeline Côté, Jérôme Tétreault, Pascal Collerette-Tremblay, Jasmin Longpré, Jean-Michel Leduc, Richard Martinez, Jean Sarret, Philippe Cavelier, Florine Synthesis and Characterization in Vitro and in Vivo of (l)‑(Trimethylsilyl)alanine Containing Neurotensin Analogues The silylated amino acid (l)-(trimethylsilyl)­alanine (TMSAla) was incorporated at the C-terminal end of the minimal biologically active neurotensin (NT) fragment, leading to the synthesis of new hexapeptide NT[8–13] analogues. Here, we assessed the ability of these new silylated NT compounds to bind to NTS1 and NTS2 receptors, promote regulation of multiple signaling pathways, induce inhibition of the ileal smooth muscle contractions, and affect distinct physiological variables, including blood pressure and pain sensation. Among the C-terminal modified analogues, compound <b>6</b> (JMV2007) carrying a TMSAla residue in position 13 exhibits a higher affinity toward NT receptors than the NT native peptide. We also found that compound <b>6</b> is effective in reversing carbachol-induced contraction in the isolated strip preparation assay and at inducing a drop in blood pressure. Finally, compound <b>6</b> produces potent analgesia in experimental models of acute and persistent pain. compound 6;analogue;blood pressure;JMV;NTS 2 receptors;position 13 exhibits;contraction;silylated NT compounds;TMSAla;strip preparation assay 2015-10-08
    https://acs.figshare.com/articles/journal_contribution/Synthesis_and_Characterization_in_Vitro_and_in_Vivo_of_l_Trimethylsilyl_alanine_Containing_Neurotensin_Analogues/2123896
10.1021/acs.jmedchem.5b00841.s001