{"id":"https://openalex.org/W1995513802","doi":"https://doi.org/10.1021/jm990559d","title":"Design and Synthesis of Conformationally Constrained Glucagon Analogues","display_name":"Design and Synthesis of Conformationally Constrained Glucagon Analogues","publication_year":2000,"publication_date":"2000-04-06","ids":{"openalex":"https://openalex.org/W1995513802","doi":"https://doi.org/10.1021/jm990559d","mag":"1995513802","pmid":"https://pubmed.ncbi.nlm.nih.gov/10794689"},"language":"en","primary_location":{"id":"doi:10.1021/jm990559d","doi":"https://doi.org/10.1021/jm990559d","is_oa":false,"landing_page_url":"https://doi.org/10.1021/jm990559d","pdf_url":null,"source":{"id":"https://openalex.org/S162030435","display_name":"Journal of Medicinal Chemistry","issn_l":"0022-2623","issn":["0022-2623","1520-4804"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","jufo-3","ki-jl-2","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"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":"Journal of Medicinal Chemistry","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/A5103852963","display_name":"Dev B. Trivedi","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I138006243","display_name":"University of Arizona","ror":"https://ror.org/03m2x1q45","country_code":"US","type":"education","lineage":["https://openalex.org/I138006243"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Dev Trivedi","raw_affiliation_strings":["Departments of Chemistry and Pharmaceutical Sciences, University of Arizona, Tucson, Arizona 85721"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Chemistry and Pharmaceutical Sciences, University of Arizona, Tucson, Arizona 85721","institution_ids":["https://openalex.org/I138006243"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5111956443","display_name":"Ying Lin","orcid":"https://orcid.org/0009-0008-5605-7969","observed_orcids":["https://orcid.org/0009-0008-5605-7969"]},"institutions":[{"id":"https://openalex.org/I138006243","display_name":"University of Arizona","ror":"https://ror.org/03m2x1q45","country_code":"US","type":"education","lineage":["https://openalex.org/I138006243"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ying Lin","raw_affiliation_strings":["Departments of Chemistry and Pharmaceutical Sciences, University of Arizona, Tucson, Arizona 85721"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Chemistry and Pharmaceutical Sciences, University of Arizona, Tucson, Arizona 85721","institution_ids":["https://openalex.org/I138006243"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5081196478","display_name":"Jung\u2010Mo Ahn","orcid":"https://orcid.org/0000-0002-9104-525X","observed_orcids":["https://orcid.org/0000-0002-9104-525X"]},"institutions":[{"id":"https://openalex.org/I138006243","display_name":"University of Arizona","ror":"https://ror.org/03m2x1q45","country_code":"US","type":"education","lineage":["https://openalex.org/I138006243"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jung-Mo Ahn","raw_affiliation_strings":["Departments of Chemistry and Pharmaceutical Sciences, University of Arizona, Tucson, Arizona 85721"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Chemistry and Pharmaceutical Sciences, University of Arizona, Tucson, Arizona 85721","institution_ids":["https://openalex.org/I138006243"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5010907118","display_name":"Mara Siegel","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I138006243","display_name":"University of Arizona","ror":"https://ror.org/03m2x1q45","country_code":"US","type":"education","lineage":["https://openalex.org/I138006243"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Mara Siegel","raw_affiliation_strings":["Departments of Chemistry and Pharmaceutical Sciences, University of Arizona, Tucson, Arizona 85721"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Chemistry and Pharmaceutical Sciences, University of Arizona, Tucson, Arizona 85721","institution_ids":["https://openalex.org/I138006243"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5038449827","display_name":"Nevena N. Mollova","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I138006243","display_name":"University of Arizona","ror":"https://ror.org/03m2x1q45","country_code":"US","type":"education","lineage":["https://openalex.org/I138006243"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Nevena N. Mollova","raw_affiliation_strings":["Departments of Chemistry and Pharmaceutical Sciences, University of Arizona, Tucson, Arizona 85721"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Chemistry and Pharmaceutical Sciences, University of Arizona, Tucson, Arizona 85721","institution_ids":["https://openalex.org/I138006243"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5050053546","display_name":"Karl H. Schram","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I138006243","display_name":"University of Arizona","ror":"https://ror.org/03m2x1q45","country_code":"US","type":"education","lineage":["https://openalex.org/I138006243"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Karl H. Schram","raw_affiliation_strings":["Departments of Chemistry and Pharmaceutical Sciences, University of Arizona, Tucson, Arizona 85721"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Chemistry and Pharmaceutical Sciences, University of Arizona, Tucson, Arizona 85721","institution_ids":["https://openalex.org/I138006243"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5076760321","display_name":"Victor J. Hruby","orcid":"https://orcid.org/0000-0001-9386-8412","observed_orcids":["https://orcid.org/0000-0001-9386-8412"]},"institutions":[{"id":"https://openalex.org/I138006243","display_name":"University of Arizona","ror":"https://ror.org/03m2x1q45","country_code":"US","type":"education","lineage":["https://openalex.org/I138006243"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Victor J. Hruby","raw_affiliation_strings":["Departments of Chemistry and Pharmaceutical Sciences, University of Arizona, Tucson, Arizona 85721"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Chemistry and Pharmaceutical Sciences, University of Arizona, Tucson, Arizona 85721","institution_ids":["https://openalex.org/I138006243"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5076760321"],"corresponding_institution_ids":["https://openalex.org/I138006243"],"apc_list":{"value":4500,"currency":"USD","value_usd":4500},"apc_paid":null,"fwci":0.722,"has_fulltext":false,"cited_by_count":20,"citation_normalized_percentile":{"value":0.66947298,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":96},"biblio":{"volume":"43","issue":"9","first_page":"1714","last_page":"1722"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10911","display_name":"Chemical Synthesis and Analysis","score":0.8467000126838684,"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/T10911","display_name":"Chemical Synthesis and Analysis","score":0.8467000126838684,"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/T10839","display_name":"Pancreatic function and diabetes","score":0.039400000125169754,"subfield":{"id":"https://openalex.org/subfields/2746","display_name":"Surgery"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10835","display_name":"Carbohydrate Chemistry and Synthesis","score":0.039000000804662704,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/glucagon-analogues","display_name":"glucagon analogues","score":0.9229999780654907},{"id":"https://openalex.org/keywords/conformationally-constrained-peptides","display_name":"conformationally constrained peptides","score":0.8109999895095825},{"id":"https://openalex.org/keywords/lactam-bridge","display_name":"lactam bridge","score":0.9110000133514404},{"id":"https://openalex.org/keywords/glucagon-receptor","display_name":"glucagon receptor","score":0.824999988079071},{"id":"https://openalex.org/keywords/receptor-antagonists","display_name":"receptor antagonists","score":0.7440000176429749},{"id":"https://openalex.org/keywords/partial-agonists","display_name":"partial agonists","score":0.9900000095367432},{"id":"https://openalex.org/keywords/adenylyl-cyclase-activity","display_name":"adenylate cyclase activity","score":0.8659999966621399},{"id":"https://openalex.org/keywords/receptor-binding-affinity","display_name":"receptor binding affinity","score":0.8510000109672546},{"id":"https://openalex.org/keywords/circular-dichroism","display_name":"circular dichroism","score":0.7379999756813049},{"id":"https://openalex.org/keywords/molecular-modeling","display_name":"molecular modeling","score":0.8389999866485596},{"id":"https://openalex.org/keywords/peptide-synthesis","display_name":"peptide synthesis","score":0.4309999942779541}],"concepts":[{"id":"https://openalex.org/C2778563252","wikidata":"https://www.wikidata.org/wiki/Q170617","display_name":"Glucagon","level":3,"score":0.9434995651245117},{"id":"https://openalex.org/C2780069284","wikidata":"https://www.wikidata.org/wiki/Q5198121","display_name":"Cyclase","level":3,"score":0.8169549107551575},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.8054630756378174},{"id":"https://openalex.org/C180526460","wikidata":"https://www.wikidata.org/wiki/Q356240","display_name":"Adenylate kinase","level":3,"score":0.7809301614761353},{"id":"https://openalex.org/C2778542361","wikidata":"https://www.wikidata.org/wiki/Q14904911","display_name":"Glucagon receptor","level":4,"score":0.7512124180793762},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.629120409488678},{"id":"https://openalex.org/C163235415","wikidata":"https://www.wikidata.org/wiki/Q899814","display_name":"Second messenger system","level":3,"score":0.5601062774658203},{"id":"https://openalex.org/C133571119","wikidata":"https://www.wikidata.org/wiki/Q899102","display_name":"Circular dichroism","level":2,"score":0.5216336846351624},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.4318525791168213},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.4155523180961609},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.4035893678665161},{"id":"https://openalex.org/C71315377","wikidata":"https://www.wikidata.org/wiki/Q11364","display_name":"Hormone","level":2,"score":0.07849523425102234}],"mesh":[{"descriptor_ui":"D000595","descriptor_name":"Amino Acid Sequence","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002462","descriptor_name":"Cell Membrane","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D002462","descriptor_name":"Cell Membrane","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D002851","descriptor_name":"Chromatography, High Pressure Liquid","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002855","descriptor_name":"Chromatography, Thin Layer","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002942","descriptor_name":"Circular Dichroism","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005765","descriptor_name":"Gastrointestinal Agents","qualifier_ui":"Q000138","qualifier_name":"chemical synthesis","is_major_topic":true},{"descriptor_ui":"D005934","descriptor_name":"Glucagon","qualifier_ui":"Q000031","qualifier_name":"analogs & derivatives","is_major_topic":true},{"descriptor_ui":"D005934","descriptor_name":"Glucagon","qualifier_ui":"Q000138","qualifier_name":"chemical synthesis","is_major_topic":false},{"descriptor_ui":"D008099","descriptor_name":"Liver","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","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":"D008969","descriptor_name":"Molecular Sequence Data","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011487","descriptor_name":"Protein Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015195","descriptor_name":"Drug Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016339","descriptor_name":"Spectrometry, Mass, Fast Atom Bombardment","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D017207","descriptor_name":"Rats, Sprague-Dawley","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051381","descriptor_name":"Rats","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D066298","descriptor_name":"In Vitro Techniques","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1021/jm990559d","doi":"https://doi.org/10.1021/jm990559d","is_oa":false,"landing_page_url":"https://doi.org/10.1021/jm990559d","pdf_url":null,"source":{"id":"https://openalex.org/S162030435","display_name":"Journal of Medicinal Chemistry","issn_l":"0022-2623","issn":["0022-2623","1520-4804"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","jufo-3","ki-jl-2","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"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":"Journal of Medicinal Chemistry","raw_type":"journal-article"},{"id":"pmid:10794689","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/10794689","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":"Journal of medicinal chemistry","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.504800021648407,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G863842726","display_name":null,"funder_award_id":"DK21085","funder_id":"https://openalex.org/F4320337357","funder_display_name":"National Institute of Diabetes and Digestive and Kidney Diseases"}],"funders":[{"id":"https://openalex.org/F4320337357","display_name":"National Institute of Diabetes and Digestive and Kidney Diseases","ror":"https://ror.org/00adh9b73"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":38,"referenced_works":["https://openalex.org/W255489331","https://openalex.org/W1510475440","https://openalex.org/W1601828936","https://openalex.org/W1952295494","https://openalex.org/W1964058863","https://openalex.org/W1968246808","https://openalex.org/W1976314195","https://openalex.org/W1990332976","https://openalex.org/W1990954082","https://openalex.org/W1992857468","https://openalex.org/W2003124912","https://openalex.org/W2006848444","https://openalex.org/W2010123487","https://openalex.org/W2012735547","https://openalex.org/W2022761661","https://openalex.org/W2035919768","https://openalex.org/W2036444031","https://openalex.org/W2039911916","https://openalex.org/W2043468404","https://openalex.org/W2043513833","https://openalex.org/W2043556557","https://openalex.org/W2043607847","https://openalex.org/W2047730466","https://openalex.org/W2054048788","https://openalex.org/W2054293900","https://openalex.org/W2056541680","https://openalex.org/W2056644409","https://openalex.org/W2059255310","https://openalex.org/W2060381504","https://openalex.org/W2073647780","https://openalex.org/W2079922794","https://openalex.org/W2083560736","https://openalex.org/W2086070857","https://openalex.org/W2090086134","https://openalex.org/W2100038314","https://openalex.org/W2131124255","https://openalex.org/W2155524113","https://openalex.org/W2169503005"],"related_works":["https://openalex.org/W150410745","https://openalex.org/W2005073606","https://openalex.org/W1989258777","https://openalex.org/W2073647780","https://openalex.org/W4667958","https://openalex.org/W1594927168","https://openalex.org/W198163831","https://openalex.org/W1488257827","https://openalex.org/W2086070857","https://openalex.org/W2335042048"],"abstract_inverted_index":{"Glucagon":[0],"was":[1],"systematically":[2],"modified":[3],"by":[4,59],"forming":[5],"lactam":[6],"bridges":[7],"within":[8],"the":[9,13,98,103,138,166,171,183],"central":[10],"region":[11],"of":[12,83,102,141],"molecule":[14],"to":[15,108,114],"give":[16],"conformationally":[17],"constrained":[18],"cyclic":[19,22,104],"analogues.":[20],"Six":[21],"glucagon":[23,84,185],"analogues":[24,75,90,105],"have":[25,109],"been":[26],"designed":[27],"and":[28,45,52,63,79,92,132,146,180],"synthesized.":[29],"They":[30],"are":[31],"c[Asp(9),Lys(12)][Lys(17,18),":[32],"Glu(21)]glucagon-NH(2)":[33,43],"(1),":[34],"c[Asp(9),Lys(12)]glucagon-NH(2)":[35],"(2),":[36],"c[Lys(12),Asp(15)]glucagon-NH(2)":[37],"(3),":[38],"c[Asp(15),":[39],"Lys(18)]glucagon-NH(2)":[40],"(4),":[41],"[Lys(17)-c[Lys(18),":[42],"(5),":[44],"c[Lys(12),Asp(21)]glucagon-NH(2)":[46],"(6).":[47],"The":[48,116],"receptor":[49,53,143],"binding":[50,61,111,144],"potencies":[51,112],"second":[54],"messenger":[55],"activities":[56],"were":[57,81,94,106,126],"determined":[58],"radio-receptor":[60],"assays":[62],"adenylate":[64,86],"cyclase":[65,87,149],"assays,":[66],"respectively,":[67],"using":[68,128],"rat":[69],"liver":[70],"plasma":[71],"membranes.":[72],"Most":[73],"interestingly,":[74],"1,":[76],"2,":[77],"3,":[78],"4":[80],"antagonists":[82],"stimulated":[85],"activity,":[88],"whereas":[89],"5":[91],"6":[93],"partial":[95],"agonists":[96],"in":[97,158],"functional":[99],"assay.":[100],"All":[101],"found":[107],"reduced":[110],"relative":[113],"glucagon.":[115],"structural":[117],"features":[118],"that":[119,151,165],"might":[120],"be":[121],"responsible":[122],"for":[123,177],"these":[124],"effects":[125],"studied":[127],"circular":[129],"dichroism":[130],"spectroscopy":[131],"molecular":[133,168,178],"modeling.":[134],"These":[135,162],"results":[136],"demonstrated":[137],"significant":[139],"modulations":[140],"both":[142],"affinity":[145],"transduction":[147,181],"(adenylate":[148],"activity)":[150],"can":[152],"accompany":[153],"regional":[154],"conformational":[155],"constraints":[156],"even":[157],"larger":[159],"polypeptide":[160],"ligands.":[161],"studies":[163],"suggest":[164],"entire":[167],"conformation,":[169],"including":[170],"flexible":[172],"middle":[173],"portion,":[174],"is":[175],"important":[176],"recognition":[179],"at":[182],"hepatic":[184],"receptor.":[186]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2025,"cited_by_count":1},{"year":2019,"cited_by_count":1},{"year":2016,"cited_by_count":1},{"year":2015,"cited_by_count":1},{"year":2014,"cited_by_count":1},{"year":2013,"cited_by_count":2}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-06-24T00:00:00"}