English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/60856
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
Title

Structure-activity relationship study of opiorphin, a human dual ectopeptidase inhibitor with antinociceptive properties

AuthorsRosa, Mónica; Arsequell, Gemma; Rougeot, Catherine; Calle Jiménez, Luis Pablo ; Marcelo, Filipa ; Pinto, Marta; Centeno, Nuria B.; Jiménez-Barbero, Jesús ; Valencia, Gregorio
Issue Date9-Feb-2012
PublisherAmerican Chemical Society
CitationJournal of Medicinal Chemistry 55(3):1181-1188 (2012)
AbstractToward developing new potential analgesics, this first structure–activity relationship study of opiorphin (H-Gln-Arg-Phe-Ser-Arg-OH), a human peptide inhibiting enkephalin degradation, was performed. A systematic Ala scanning proved that Phe3 is a key residue for neprilysin and aminopeptidase N (AP-N) ectoenkephalinase inhibition. A series of Phe3-halogenated analogues revealed that halogen bonding based optimization strategies are not applicable to this residue. Additional substituted Phe3 derivatives showed that replacing l-Phe3 for d-Phe3 increased the AP-N inhibition potency by 1 order of magnitude. NMR studies and molecular mechanics calculations indicated that the improved potency may be due to CH−π stacking interactions between the aromatic ring of d-Phe3 and the Hγ protons of Arg2. This structural motif is not possible for the native opiorphin and may be useful for the design of further potent and metabolically stable analogues
Description8 páginas, 4 figuras, 3 tablas, 1 esquema -- PAGS nros. 1181-1188
URIhttp://hdl.handle.net/10261/60856
DOI10.1021/jm2012112
ISSN0022-2623
E-ISSN1520-4804
Appears in Collections:(CIB) Artículos
Files in This Item:
File Description SizeFormat 
restringido.pdf21,67 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.