Arginine-Based Inhibitors of Nitric Oxide Synthase Therapeutic Potential and Challenges英文文献资料.docVIP

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Arginine-Based Inhibitors of Nitric Oxide Synthase Therapeutic Potential and Challenges英文文献资料.doc

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Arginine-Based Inhibitors of Nitric Oxide Synthase Therapeutic Potential and Challenges英文文献资料

HindawiPublishingCorporation MediatorsofIn?ammation Volume2012,ArticleID318087,22pages doi:10.1155/2012/318087 ReviewArticle Arginine-BasedInhibitorsofNitricOxideSynthase: TherapeuticPotentialandChallenges JanV′?teˇcek,1,2Anton′?nLojek,2GiuseppeValacchi,3,4andLuk′aˇsKubala 1,2 1 InternationalClinicalResearchCenter-CenterofBiomolecularandCellEngineering,St.Anne’sUniversityHospitalBrno, 65691Brno,CzechRepublic 2 3 4 InstituteofBiophysics,AcademyofSciencesoftheCzechRepublic,61265Brno,CzechRepublic DepartmentofEvolutionaryBiology,UniversityofFerrara,44100Ferrara,Italy DepartmentofFoodandNutrition,KyungHeeUniversity,Seoul130-701,RepublicofKorea CorrespondenceshouldbeaddressedtoLuk′aˇsKubala,kubalal@ibp.cz Received2April2012;Accepted30May2012 AcademicEditor:HiddeBult Copyright?2012JanV′?teˇceketal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense, whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. Inthepastthreedecades,nitricoxidehasbeenwellestablishedasanimportantbioactivemoleculeimplicatedinregulationof cardiovascular,nervous,andimmunesystems.Therefore,itisnotsurprisingthatmuche?orthasbeenmadeto?ndspeci?c inhibitors of nitric oxide synthases (NOS), the enzymes responsible for production of nitric oxide. Among the many NOS inhibitorsdevelopedtodate,inhibitorsbasedonderivativesandanaloguesofarginineareofspecialinterest,asthiscategory includesarelativelyhighnumberofcompoundswithgoodpotentialforexperimentalaswellasclinicalapplication.Though thisgroupofinhibitorscoversearlynonspeci?ccompounds,moderndrugdesignstrategiessuchasbiochemicalscreeningand computer-aideddrugdesignhaveprovidedNOS-isoform-speci?cinhibitors.Withanemphasisonmajoradvancesinthis?eld, acomprehensivelistofinhibitorsbasedontheirstructuralcharacteristicsisdiscussedinthispaper.Weprovideasummaryof theirbiochemicalpropertiesaswellastheirobservede?ectsbothinvitroandinvivo.Furthermore,wefocusinparticularontheir pharmacologyanduse