title: Influence of polar side chains modifications on the dual enkephalinase inhibitory activity and conformation of human opiorphin, a pain perception related peptide.
abstract: The dual inhibitory action of the pain related peptide opiorphin (H-Gln-Arg-Phe-Ser-Arg-OH) against neutral endopeptidase (NEP) and aminopeptidase N (AP-N) was further investigated by a SAR study involving minor modifications on the polar side chains of Arg residues and glycosylation with monosaccharides at Ser. None of them exerted dual or individual inhibitory potency superior than opiorphin. However, the correlations deduced offer further proof for the key role of these residues upon the binding and bioactive conformational stabilization of opiorphin. NMR conformational studies on the glycopeptides suggest that they are still very flexible compounds that may attain their respective bioactive conformations.
authors.affiliation: Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), E-08034 Barcelona, Spain.
authors.forename: Mònica
authors.initials: M
authors.lastname: Rosa
authors.affiliation: UCIBIO, REQUIMTE Faculdade Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
authors.forename: Filipa
authors.initials: F
authors.lastname: Marcelo
authors.affiliation: CIC bioGUNE, Bizkaia Technological Park, E-48160 Derio, Spain.
authors.forename: Luis P
authors.initials: LP
authors.lastname: Calle
authors.affiliation: Institut Pasteur-Unité de Biochimie Structurale et Cellulaire/URA2185-CNRS, Paris Cedex 15 75724, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Rougeot
authors.affiliation: CIC bioGUNE, Bizkaia Technological Park, E-48160 Derio, Spain; Ikerbasque, Basque Foundation for Science, E-48013 Bilbao, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Jiménez-Barbero
authors.affiliation: Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), E-08034 Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Arsequell
authors.affiliation: Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), E-08034 Barcelona, Spain.
authors.forename: Gregorio
authors.initials: G
authors.lastname: Valencia
mesh_terms: D000116:Acetylgalactosamine / Q000737:chemistry; D000117:Acetylglucosamine / Q000737:chemistry; D019943:Amino Acid Substitution; D001120:Arginine / Q000737:chemistry; D018826:CD13 Antigens / Q000037:antagonists & inhibitors*; D006020:Glycopeptides / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D009842:Oligopeptides / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D012471:Salivary Proteins and Peptides / Q000737:chemistry*; D012694:Serine / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D006020:Glycopeptides; D009842:Oligopeptides; D012471:Salivary Proteins and Peptides; C517879:glutaminyl-arginyl-phenylalanyl-seryl-arginine; D012694:Serine; D001120:Arginine; D018826:CD13 Antigens; D015260:Neprilysin; D000116:Acetylgalactosamine; D000117:Acetylglucosamine
keywords: AP-N; Glycopeptides pain; Neutral endopeptidase; Opiorphin analogs; SAR study