Synthesis and Characterization in Vitro and in Vivo of (l)-(Trimethylsilyl)alanine Containing Neurotensin Analogues.

摘要: The silylated amino acid (l)-(trimethylsilyl)alanine (TMSAla) was incorporated at the C-terminal end of minimal biologically active neurotensin (NT) fragment, leading to synthesis new hexapeptide NT[8–13] analogues. Here, we assessed ability these NT compounds bind NTS1 and NTS2 receptors, promote regulation multiple signaling pathways, induce inhibition ileal smooth muscle contractions, affect distinct physiological variables, including blood pressure pain sensation. Among modified analogues, compound 6 (JMV2007) carrying a TMSAla residue in position 13 exhibits higher affinity toward receptors than native peptide. We also found that is effective reversing carbachol-induced contraction isolated strip preparation assay inducing drop pressure. Finally, produces potent analgesia experimental models acute persistent pain.