Author/Authors :
Ludmila Polevaya، نويسنده , , Thomas Mavromoustakos، نويسنده , , Panagiotis Zoumboulakis، نويسنده , , Simona Golic Grdadolnik، نويسنده , , Panagiota Roumelioti، نويسنده , , Nektarios Giatas، نويسنده , , Ilze Mutule، نويسنده , , Tatjana Keivish، نويسنده , , Demetrios V. Vlahakos، نويسنده , , Efstathios K. Iliodromitis، نويسنده , , Dimitrios Th. Kremastinos، نويسنده , , John Matsoukas، نويسنده ,
Abstract :
The novel amide linked Angiotensin II (ANG II) cyclic analogue cyclo(3, 5) -[Sar1-Lys3-Glu5-Ile8] ANG II (18) has been designed, synthesized and bioassayed in anesthetized rabbits. The constrained cyclic analogue with a lactam amide bridge linking a Lys-Glu pair at positions 3 and 5 and possessing Ile at position 8, was synthesized by solution procedure using the maximum protection strategy. This analogue was found to be inhibitor of Angiotensin II. NMR spectroscopy coupled with computational analysis showed clustering between the side chains of the key aminoacids Tyr4-His6-Ile8 similar to that observed with ANG II. The obtained data show that only π*–π* interactions observed in ANG II or its superagonist Sar1 [ANG II] are missing. Therefore, it can be concluded that these interactions are essential for agonist activity. Conformational analysis comparisons between AT1 antagonists losartan, eprosartan and irbesartan with C-terminal segment of cyclic compound 18 revealed structural similarities.
