Novel GnRH I and II analogues were designed and synthesized by Solid Phase Peptides Synthesis (SPPS), since GnRH has antiproliferative property, but poor metabolic stability. To rationalize synthetic difficulties, molecular dynamics simulations were performed, showing the conformational behavior of three derivatives. Among the two peptidomimetics series (Ie,f and IIe,f , GnRH I and GnRH II analogues respectively) several compounds (Id-f and IIc-e) showed a significant binding affinity. In particular, derivative Ie has an increased metabolic stability with respect to the physiological ligand (Ie t1/2= 3.96 h versus GnRH I t1/2 = 2.63 h).
Novel peptidomimetics related to Gonadotropin releasing hormone (GnRH) / A. Gelain, L. Rizzi, L. Legnani, A. Pacini, K. Spyridaki, V. Karageorgos, G. Liapakis, S. Villa. - In: MEDCHEMCOMM. - ISSN 2040-2503. - 6:9(2015), pp. 1656-1665.
|Titolo:||Novel peptidomimetics related to Gonadotropin releasing hormone (GnRH)|
GELAIN, ARIANNA (Primo)
VILLA, STEFANIA (Corresponding)
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
Settore CHIM/06 - Chimica Organica
|Data di pubblicazione:||2015|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1039/C5MD00259A|
|Appare nelle tipologie:||01 - Articolo su periodico|