Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Morpholino, Piperidino, and Pyrrolidino Derivatives of Pyrimidine Nucleosides as Inhibitors of Ribonuclease A: Synthesis, Biochemical, and Crystallographic Evaluation
Δημιουργός/Συγγραφέας:	Samanta, Anirban [EL] Λεωνίδας, Δημήτρης Δ.[EN] Leonidas, Demetres D. Dasgupta, Swagata Pathak, Tanmaya [EL] Ζωγράφος, Σπύρος Ε.[EN] Zographos, Spyros E. [EL] Οικονομάκος, Νίκος Γ.[EN] Oikonomakos, Nikos G.
Εκδότης:	American Chemical Society
Τόπος έκδοσης:	WASHINGTON
Ημερομηνία:	2009-02-26
Γλώσσα:	Αγγλικά
ISSN:	0022-2623
DOI:	10.1021/jm800724t
Περίληψη:	Six 5'-deoxy-5'-morpholine, piperidine, and pyrrolidine of pyrimidine nucleosides have been synthesized and characterized. Their inhibitory action to ribonuclease A has been studied by biochemical analysis and X-ray crystallography. These compounds are moderate inhibitors of RNase A with mid-to-upper micromolar inhibition constants (K(i)). The high resolution X-ray crystal structures of the RNase A-inhibitor complexes have shown that all inhibitors bind at the enzyme catalytic cleft with the pyrimidine nucleobase at the B(1)R(2) subsites while the 5' group binds away from the main subsite P1, where P-O(5') bond cleavage occurs, toward the solvent close to subsite P(0). Structure-activity relationship analysis has demonstrated that the compounds with the larger group in the 5' position are more potent. Comparative structural analysis of these RNase A complexes with other similar RNase A-ligand complexes provides a structural explanation of their potency and suggests ways to improve their efficiency and selectivity. These inhibitors can be the starting point for the development of compounds that can be used as pharmaceuticals against pathologies associated with RNase A homologues such as human angiogemn, which is implicated in tumor induced neovascularization.
Τίτλος πηγής δημοσίευσης:	Journal of Medicinal Chemistry
Τόμος/Κεφάλαιο:	52
Τεύχος:	4
Σελίδες:	932-942
Θεματική Κατηγορία:	[EL] Χημεία (Γενικά)[EN] Chemistry (General) [EL] Φαρμακευτική[EN] Pharmacy and materia medica
Λέξεις-Κλειδιά:	Chemistry, Medicinal
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© AMER CHEMICAL SOC
Ηλεκτρονική διεύθυνση περιοδικού (link) :	http://pubs.acs.org/jmc
ΙΒΦΧΒ: αρχειακή συλλογή:	Ινστιτούτο Οργανικής και Φαρμακευτικής Χημείας (ΙΟΦΧ) (έως 2012)
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο