title: S-nitrosophytochelatins: investigation of the bioactivity of an oligopeptide nitric oxide delivery system.
abstract: This study investigates the in vitro bioactivity of S-nitrosophytochelatins (SNOPCs), oligopeptide analogues of S-nitrosoglutathione (GSNO), and their mechanisms of nitric oxide (NO) delivery. SNOPCs were more potent than GSNO in inhibiting platelet aggregation and stimulating vasorelaxation. Their potency was related to the number of S-nitrosated moieties per mole compound. Transnitrosation reactions with cell membrane surface components were shown to be the primary mode of NO delivery to intracellular targets for SNOPCs, while delivery via γ-glutamyl transpeptidase was unique to GSNO. Due to rapid NO release, larger SNOPCs elicited a more transitory effect compared to smaller compounds. The duration of effect was influenced by compound molecular weight, NO release kinetics, ability to undergo transnitrosation, and incubation time with tissues. In summary, a new oligopeptide NO delivery system based on SNOPCs was shown to be biologically active and can be used to investigate the mechanisms of NO delivery to intracellular targets.
authors.affiliation: Institute of Pharmaceutical Science, King's College London, London, SE1 9NH, UK.
authors.forename: Lamia
authors.initials: L
authors.lastname: Heikal
authors.forename: Philip I
authors.initials: PI
authors.lastname: Aaronson
authors.forename: Albert
authors.initials: A
authors.lastname: Ferro
authors.forename: Manasi
authors.initials: M
authors.lastname: Nandi
authors.forename: Gary P
authors.initials: GP
authors.lastname: Martin
authors.forename: Lea Ann
authors.initials: LA
authors.lastname: Dailey
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D001692:Biological Transport / Q000187:drug effects; D040761:Biomimetic Materials / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D054811:Phytochelatins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D026422:S-Nitrosoglutathione / Q000031:analogs & derivatives / Q000494:pharmacology*; D046509:Tissue Culture Techniques; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D054811:Phytochelatins; D005723:gamma-Glutamyltransferase