{"id":"https://openalex.org/W1983874809","doi":"https://doi.org/10.1021/bi0119823","title":"A Nonhydrolyzable Reactive cAMP Analogue, (Sp)-8-[(4-Bromo-2,3-dioxobutyl)thio]adenosine 3\u2018,5\u2018-Cyclic S-(Methyl)monophosphorothioate, Irreversibly Inactivates Human Platelet cGMP-Inhibited cAMP Phosphodiesterase at Micromolar Concentrations","display_name":"A Nonhydrolyzable Reactive cAMP Analogue, (Sp)-8-[(4-Bromo-2,3-dioxobutyl)thio]adenosine 3\u2018,5\u2018-Cyclic S-(Methyl)monophosphorothioate, Irreversibly Inactivates Human Platelet cGMP-Inhibited cAMP Phosphodiesterase at Micromolar Concentrations","publication_year":2002,"publication_date":"2002-02-05","ids":{"openalex":"https://openalex.org/W1983874809","doi":"https://doi.org/10.1021/bi0119823","mag":"1983874809","pmid":"https://pubmed.ncbi.nlm.nih.gov/11863434"},"language":"en","primary_location":{"id":"doi:10.1021/bi0119823","doi":"https://doi.org/10.1021/bi0119823","is_oa":false,"landing_page_url":"https://doi.org/10.1021/bi0119823","pdf_url":null,"source":{"id":"https://openalex.org/S104038378","display_name":"Biochemistry","issn_l":"0006-2960","issn":["0006-2960","1520-4995","1943-295X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-100","russia-white-list-2"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Biochemistry","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5038966582","display_name":"Su H. Hung","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I84392919","display_name":"Temple University","ror":"https://ror.org/00kx1jb78","country_code":"US","type":"education","lineage":["https://openalex.org/I84392919"]},{"id":"https://openalex.org/I86501945","display_name":"University of Delaware","ror":"https://ror.org/01sbq1a82","country_code":"US","type":"education","lineage":["https://openalex.org/I86501945"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Su H. Hung","raw_affiliation_strings":["Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, and Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, and Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716","institution_ids":["https://openalex.org/I84392919","https://openalex.org/I86501945"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5057893755","display_name":"K. S. Madhusoodanan","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I84392919","display_name":"Temple University","ror":"https://ror.org/00kx1jb78","country_code":"US","type":"education","lineage":["https://openalex.org/I84392919"]},{"id":"https://openalex.org/I86501945","display_name":"University of Delaware","ror":"https://ror.org/01sbq1a82","country_code":"US","type":"education","lineage":["https://openalex.org/I86501945"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"K. S. Madhusoodanan","raw_affiliation_strings":["Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, and Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, and Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716","institution_ids":["https://openalex.org/I84392919","https://openalex.org/I86501945"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Robert L. Boyd","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I84392919","display_name":"Temple University","ror":"https://ror.org/00kx1jb78","country_code":"US","type":"education","lineage":["https://openalex.org/I84392919"]},{"id":"https://openalex.org/I86501945","display_name":"University of Delaware","ror":"https://ror.org/01sbq1a82","country_code":"US","type":"education","lineage":["https://openalex.org/I86501945"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Robert L. Boyd","raw_affiliation_strings":["Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, and Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, and Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716","institution_ids":["https://openalex.org/I84392919","https://openalex.org/I86501945"]}]},{"author_position":"middle","author":{"id":null,"display_name":"James L. Baldwin","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I84392919","display_name":"Temple University","ror":"https://ror.org/00kx1jb78","country_code":"US","type":"education","lineage":["https://openalex.org/I84392919"]},{"id":"https://openalex.org/I86501945","display_name":"University of Delaware","ror":"https://ror.org/01sbq1a82","country_code":"US","type":"education","lineage":["https://openalex.org/I86501945"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"James L. Baldwin","raw_affiliation_strings":["Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, and Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, and Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716","institution_ids":["https://openalex.org/I84392919","https://openalex.org/I86501945"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5111830511","display_name":"Roberta F. Colman","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I84392919","display_name":"Temple University","ror":"https://ror.org/00kx1jb78","country_code":"US","type":"education","lineage":["https://openalex.org/I84392919"]},{"id":"https://openalex.org/I86501945","display_name":"University of Delaware","ror":"https://ror.org/01sbq1a82","country_code":"US","type":"education","lineage":["https://openalex.org/I86501945"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Roberta F. Colman","raw_affiliation_strings":["Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, and Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, and Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716","institution_ids":["https://openalex.org/I84392919","https://openalex.org/I86501945"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5104652394","display_name":"Robert W. Colman","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I84392919","display_name":"Temple University","ror":"https://ror.org/00kx1jb78","country_code":"US","type":"education","lineage":["https://openalex.org/I84392919"]},{"id":"https://openalex.org/I86501945","display_name":"University of Delaware","ror":"https://ror.org/01sbq1a82","country_code":"US","type":"education","lineage":["https://openalex.org/I86501945"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Robert W. Colman","raw_affiliation_strings":["Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, and Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, and Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716","institution_ids":["https://openalex.org/I84392919","https://openalex.org/I86501945"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":4500,"currency":"USD","value_usd":4500},"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":2,"citation_normalized_percentile":{"value":0.09593191,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"41","issue":"9","first_page":"2962","last_page":"2969"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12434","display_name":"Phosphodiesterase function and regulation","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T12434","display_name":"Phosphodiesterase function and regulation","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11748","display_name":"Organophosphorus compounds synthesis","score":0.00019999999494757503,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T12827","display_name":"Biochemical and Molecular Research","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/phosphodiesterase-3a","display_name":"PDE3A","score":0.7770000100135803},{"id":"https://openalex.org/keywords/camp-phosphodiesterase","display_name":"cAMP phosphodiesterase","score":0.8629999756813049},{"id":"https://openalex.org/keywords/platelets","display_name":"platelets","score":0.43700000643730164},{"id":"https://openalex.org/keywords/irreversible-enzyme-inactivation","display_name":"irreversible enzyme inactivation","score":0.7879999876022339},{"id":"https://openalex.org/keywords/affinity-reagents","display_name":"affinity reagents","score":0.6840000152587891},{"id":"https://openalex.org/keywords/active-site","display_name":"active site","score":0.47099998593330383},{"id":"https://openalex.org/keywords/site-directed-mutants","display_name":"site-directed mutants","score":0.5789999961853027},{"id":"https://openalex.org/keywords/camp-hydrolysis","display_name":"cAMP hydrolysis","score":0.531000018119812},{"id":"https://openalex.org/keywords/molecular-docking","display_name":"molecular docking","score":0.4790000021457672},{"id":"https://openalex.org/keywords/enzyme-kinetics","display_name":"enzyme kinetics","score":0.34599998593330383},{"id":"https://openalex.org/keywords/camp","display_name":"cyclic AMP","score":0.49799999594688416},{"id":"https://openalex.org/keywords/cgmp","display_name":"cyclic GMP","score":0.9480000138282776},{"id":"https://openalex.org/keywords/5-amp","display_name":"5'-AMP","score":0.6499999761581421}],"concepts":[{"id":"https://openalex.org/C2781253882","wikidata":"https://www.wikidata.org/wiki/Q770860","display_name":"Thio-","level":2,"score":0.7486953735351562},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.725233793258667},{"id":"https://openalex.org/C62826618","wikidata":"https://www.wikidata.org/wiki/Q424304","display_name":"Phosphodiesterase","level":3,"score":0.704954981803894},{"id":"https://openalex.org/C2776991684","wikidata":"https://www.wikidata.org/wiki/Q190012","display_name":"Adenosine","level":2,"score":0.6747025847434998},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.6100853085517883},{"id":"https://openalex.org/C41183919","wikidata":"https://www.wikidata.org/wiki/Q423026","display_name":"Active site","level":3,"score":0.5304961204528809},{"id":"https://openalex.org/C512185932","wikidata":"https://www.wikidata.org/wiki/Q28745","display_name":"Nucleotide","level":3,"score":0.41947585344314575},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.39215975999832153},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.29589271545410156},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0}],"mesh":[{"descriptor_ui":"D000242","descriptor_name":"Cyclic AMP","qualifier_ui":"Q000031","qualifier_name":"analogs & derivatives","is_major_topic":false},{"descriptor_ui":"D000242","descriptor_name":"Cyclic AMP","qualifier_ui":"Q000138","qualifier_name":"chemical synthesis","is_major_topic":true},{"descriptor_ui":"D000242","descriptor_name":"Cyclic AMP","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D000242","descriptor_name":"Cyclic AMP","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001665","descriptor_name":"Binding Sites","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002460","descriptor_name":"Cell Line","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004305","descriptor_name":"Dose-Response Relationship, Drug","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007313","descriptor_name":"Insecta","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008958","descriptor_name":"Models, Molecular","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D010726","descriptor_name":"Phosphodiesterase Inhibitors","qualifier_ui":"Q000138","qualifier_name":"chemical synthesis","is_major_topic":true},{"descriptor_ui":"D010726","descriptor_name":"Phosphodiesterase Inhibitors","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D010726","descriptor_name":"Phosphodiesterase Inhibitors","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D013379","descriptor_name":"Substrate Specificity","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015105","descriptor_name":"3',5'-Cyclic-AMP Phosphodiesterases","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":true},{"descriptor_ui":"D015105","descriptor_name":"3',5'-Cyclic-AMP Phosphodiesterases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D054684","descriptor_name":"Cyclic Nucleotide Phosphodiesterases, Type 3","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1021/bi0119823","doi":"https://doi.org/10.1021/bi0119823","is_oa":false,"landing_page_url":"https://doi.org/10.1021/bi0119823","pdf_url":null,"source":{"id":"https://openalex.org/S104038378","display_name":"Biochemistry","issn_l":"0006-2960","issn":["0006-2960","1520-4995","1943-295X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-100","russia-white-list-2"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Biochemistry","raw_type":"journal-article"},{"id":"pmid:11863434","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/11863434","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Biochemistry","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":3,"referenced_works":["https://openalex.org/W1550703776","https://openalex.org/W2016066239","https://openalex.org/W4300338629"],"related_works":["https://openalex.org/W2071217711","https://openalex.org/W2056645340","https://openalex.org/W2009690525","https://openalex.org/W99370438","https://openalex.org/W1999959928","https://openalex.org/W2011993324","https://openalex.org/W3166970618","https://openalex.org/W2043141059","https://openalex.org/W1982780585","https://openalex.org/W4240184064"],"abstract_inverted_index":{"We":[0,23,133],"previously":[1],"showed":[2],"that":[3,165],"8-[(4-bromo-2,3-dioxobutyl)thio]adenosine":[4],"3',5'-cyclic":[5,33],"monophosphate":[6],"inactivates":[7,37],"cAMP":[8,30,182,201,226],"phosphodiesterase":[9],"(PDE3A);":[10],"however,":[11],"millimolar":[12],"concentrations":[13],"were":[14,85],"needed":[15],"to":[16,87,194,211],"inactivate":[17],"PDE3A":[18,38,168,206,220],"because":[19],"of":[20,50,60,76,92,96,98,104,143,167,176,219],"ongoing":[21],"hydrolysis.":[22],"have":[24],"now":[25],"synthesized":[26],"a":[27,40,48,58,174],"nonhydrolyzable":[28,74],"reactive":[29],"analogue,":[31],"(S(p))-8-[(4-bromo-2,3-dioxobutyl)thio]adenosine":[32],"S-(methyl)monophosphorothioate":[34],"(S(p)-8-BDB-TcAMPSMe).":[35],"S(p)-8-BDB-TcAMPSMe":[36,68,135,153,191],"in":[39,70,100,109,159,187,215,224],"time-dependent,":[41],"irreversible":[42,200],"manner,":[43],"exhibiting":[44],"saturation":[45],"kinetics":[46],"with":[47],"k(max)":[49],"(19.5":[51],"+/-":[52,62],"0.3)":[53],"x":[54],"10(-3)":[55],"min(-1)":[56],"and":[57,119,129,145,183,207],"K(I)":[59],"3.5":[61],"0.3":[63],"muM.":[64],"To":[65],"ascertain":[66],"whether":[67],"reacts":[69],"the":[71,77,81,90,102,140,146,156,160,170,179,188,216],"active":[72,157,189,198,217],"site,":[73],"analogues":[75],"substrate":[78],"cAMP,":[79],"or":[80],"competitive":[82],"inhibitor":[83],"cGMP,":[84],"included":[86],"protect":[88],"against":[89],"inactivation":[91,105,166],"PDE3A.":[93],"The":[94,152],"order":[95],"effectiveness":[97],"protectants":[99],"decreasing":[101],"rate":[103],"(with":[106],"K(d)":[107],"values":[108],"micromolar)":[110],"is":[111,173],"as":[112,221,223],"follows:":[113],"S(p)-cAMPS":[114],"(18)":[115],">":[116,122],"R(p)-cGMPS":[117],"(560)":[118],"S(p)-cGMPS":[120],"(1260)":[121],"5'-AMP":[123],"(17":[124],"660),":[125],"R(p)-cAMPS":[126],"(30":[127],"110),":[128],"5'-GMP":[130],"(42":[131],"170).":[132],"docked":[134],"into":[136,155],"PDE3A,":[137],"based":[138],"on":[139],"structural":[141],"model":[142],"PDE3A-cAMP":[144],"kinetic":[147],"data":[148],"from":[149],"site-directed":[150,199],"mutants.":[151],"fits":[154],"site":[158,218],"model.":[161],"These":[162],"results":[163],"suggest":[164],"by":[169],"affinity":[171,202],"reagent":[172],"consequence":[175],"reaction":[177],"at":[178],"overlap":[180],"between":[181],"cGMP":[184],"binding":[185],"regions":[186],"site.":[190],"has":[192],"proven":[193],"be":[195,209],"an":[196],"effective":[197],"label":[203],"for":[204],"platelet":[205],"can":[208],"used":[210],"identify":[212],"amino":[213],"acids":[214],"well":[222],"other":[225],"phosphodiesterases.":[227]},"counts_by_year":[],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-06-24T00:00:00"}
