[Synthesis and biological activity of cyclic and linear analogs of C-terminal fragments of neurotensin].
Using solid-phase approach, new cyclic and linear analogues of C-terminal neurotensin (NT) fragments were synthesized and their vasodepressor and miotropic activities were assayed. The cyclic structures were fixed by a peptide bond linking the lysine epsilon-amino group with the C-terminal carboxyl. Cyclization was performed by using pentafluorophenyl esters or diphenylphosphorylazide. [Phe5]-cyclo(13----6 epsilon)NT-(5-13) was found to possess high depressor activity showing certain selectivity with respect to smooth vasal muscles. Circular dichroism spectra of aqueous solutions of linear and cyclic penta- and octapeptide analogues of neurotensin indicate that the linear pentapeptide in solution adopts a folded structure, while the neurotensin fragment NT-(6-13) has an unordered structure. Cyclization of the latter fragment leads to dramatic restriction of its conformational mobility resulting in a relatively rigid structure.
D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D002942:Circular Dichroism; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009496:Neurotensin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000494:pharmacology; D011487:Protein Conformation; D051381:Rats; D013329:Structure-Activity Relationship
D010446:Peptide Fragments; D009496:Neurotensin
Sintez i biologicheskaia aktivnost' tsiklicheskikh i lineĭnykh analogov C-kontsevykh fragmentov neĭrotenzina.