[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.