{"id":"https://openalex.org/W7225774665","doi":"https://doi.org/10.1021/acs.biochem.6c00407","title":"Stabilizing Full-Length PYY for Native Y1R/Y2R Dual Agonism","display_name":"Stabilizing Full-Length PYY for Native Y1R/Y2R Dual Agonism","publication_year":2026,"publication_date":"2026-11-11","ids":{"openalex":"https://openalex.org/W7225774665","doi":"https://doi.org/10.1021/acs.biochem.6c00407"},"language":"en","primary_location":{"id":"doi:10.1021/acs.biochem.6c00407","doi":"https://doi.org/10.1021/acs.biochem.6c00407","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.biochem.6c00407","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","is_traditional":true,"indexed_in":["crossref"],"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/A5117833272","display_name":"Marina V. Spenciner","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I121934306","display_name":"Tufts University","ror":"https://ror.org/05wvpxv85","country_code":"US","type":"education","lineage":["https://openalex.org/I121934306"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Marina V. Spenciner","raw_affiliation_strings":["Tufts University , , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Tufts University , , , ,","institution_ids":["https://openalex.org/I121934306"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5095888850","display_name":"Tristan C. Dinsmore","orcid":"https://orcid.org/0009-0007-7824-2121","observed_orcids":["https://orcid.org/0009-0007-7824-2121"]},"institutions":[{"id":"https://openalex.org/I121934306","display_name":"Tufts University","ror":"https://ror.org/05wvpxv85","country_code":"US","type":"education","lineage":["https://openalex.org/I121934306"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Tristan C. Dinsmore","raw_affiliation_strings":["Tufts University , , , ,"],"raw_orcid":"https://orcid.org/0009-0007-7824-2121","affiliations":[{"raw_affiliation_string":"Tufts University , , , ,","institution_ids":["https://openalex.org/I121934306"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5074032091","display_name":"Vittorio Montanari","orcid":"https://orcid.org/0000-0002-6587-1566","observed_orcids":["https://orcid.org/0000-0002-6587-1566"]},"institutions":[{"id":"https://openalex.org/I121934306","display_name":"Tufts University","ror":"https://ror.org/05wvpxv85","country_code":"US","type":"education","lineage":["https://openalex.org/I121934306"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Vittorio Montanari","raw_affiliation_strings":["Tufts University , , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Tufts University , , , ,","institution_ids":["https://openalex.org/I121934306"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5019236825","display_name":"Martin Beinborn","orcid":"https://orcid.org/0009-0008-6329-6888","observed_orcids":["https://orcid.org/0009-0008-6329-6888"]},"institutions":[{"id":"https://openalex.org/I121934306","display_name":"Tufts University","ror":"https://ror.org/05wvpxv85","country_code":"US","type":"education","lineage":["https://openalex.org/I121934306"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Martin Beinborn","raw_affiliation_strings":["Tufts University , , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Tufts University , , , ,","institution_ids":["https://openalex.org/I121934306"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5101415805","display_name":"Krishna Kumar","orcid":"https://orcid.org/0000-0002-0548-5014","observed_orcids":["https://orcid.org/0000-0002-0548-5014"]},"institutions":[{"id":"https://openalex.org/I121934306","display_name":"Tufts University","ror":"https://ror.org/05wvpxv85","country_code":"US","type":"education","lineage":["https://openalex.org/I121934306"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Krishna Kumar","raw_affiliation_strings":["Tufts University , , , ,"],"raw_orcid":"https://orcid.org/0000-0002-0548-5014","affiliations":[{"raw_affiliation_string":"Tufts University , , , ,","institution_ids":["https://openalex.org/I121934306"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5019236825","https://openalex.org/A5101415805"],"corresponding_institution_ids":["https://openalex.org/I121934306"],"apc_list":{"value":4500,"currency":"USD","value_usd":4500},"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.0,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10814","display_name":"Neuropeptides and Animal Physiology","score":0.5059000253677368,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10814","display_name":"Neuropeptides and Animal Physiology","score":0.5059000253677368,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10911","display_name":"Chemical Synthesis and Analysis","score":0.25220000743865967,"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/T10489","display_name":"Regulation of Appetite and Obesity","score":0.07970000058412552,"subfield":{"id":"https://openalex.org/subfields/2807","display_name":"Endocrine and Autonomic Systems"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[],"concepts":[{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.6955000162124634},{"id":"https://openalex.org/C2780796126","wikidata":"https://www.wikidata.org/wiki/Q290293","display_name":"Peptide YY","level":5,"score":0.6144999861717224},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.607200026512146},{"id":"https://openalex.org/C135285700","wikidata":"https://www.wikidata.org/wiki/Q38173","display_name":"G protein-coupled receptor","level":3,"score":0.5892000198364258},{"id":"https://openalex.org/C2779281246","wikidata":"https://www.wikidata.org/wiki/Q172847","display_name":"Peptide","level":2,"score":0.586899995803833},{"id":"https://openalex.org/C2779138802","wikidata":"https://www.wikidata.org/wiki/Q418602","display_name":"Dipeptide","level":3,"score":0.4180000126361847},{"id":"https://openalex.org/C43587935","wikidata":"https://www.wikidata.org/wiki/Q1258877","display_name":"Functional selectivity","level":4,"score":0.4171999990940094},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.4101000130176544},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.39980000257492065},{"id":"https://openalex.org/C14527384","wikidata":"https://www.wikidata.org/wiki/Q4693403","display_name":"Agonism","level":3,"score":0.37529999017715454},{"id":"https://openalex.org/C2778938600","wikidata":"https://www.wikidata.org/wiki/Q389934","display_name":"Agonist","level":3,"score":0.3549000024795532},{"id":"https://openalex.org/C116569031","wikidata":"https://www.wikidata.org/wiki/Q899107","display_name":"Ligand (biochemistry)","level":3,"score":0.35089999437332153},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.34700000286102295},{"id":"https://openalex.org/C16613235","wikidata":"https://www.wikidata.org/wiki/Q285982","display_name":"Endogeny","level":2,"score":0.32120001316070557},{"id":"https://openalex.org/C193042331","wikidata":"https://www.wikidata.org/wiki/Q1772003","display_name":"Structure\u2013activity relationship","level":3,"score":0.30720001459121704},{"id":"https://openalex.org/C118303440","wikidata":"https://www.wikidata.org/wiki/Q419968","display_name":"Neuropeptide","level":3,"score":0.30250000953674316},{"id":"https://openalex.org/C107824862","wikidata":"https://www.wikidata.org/wiki/Q616005","display_name":"Binding site","level":2,"score":0.2883000075817108},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.2824999988079071},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.28200000524520874},{"id":"https://openalex.org/C51639874","wikidata":"https://www.wikidata.org/wiki/Q167149","display_name":"Plasma protein binding","level":2,"score":0.27459999918937683},{"id":"https://openalex.org/C38533456","wikidata":"https://www.wikidata.org/wiki/Q1671589","display_name":"Intrinsic activity","level":4,"score":0.263700008392334},{"id":"https://openalex.org/C56191518","wikidata":"https://www.wikidata.org/wiki/Q416997","display_name":"Peptide hormone","level":3,"score":0.25209999084472656},{"id":"https://openalex.org/C160262196","wikidata":"https://www.wikidata.org/wiki/Q5376331","display_name":"Endogenous agonist","level":5,"score":0.251800000667572}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1021/acs.biochem.6c00407","doi":"https://doi.org/10.1021/acs.biochem.6c00407","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.biochem.6c00407","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"}],"best_oa_location":null,"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":44,"referenced_works":["https://openalex.org/W1964046622","https://openalex.org/W2007499400","https://openalex.org/W2013184139","https://openalex.org/W2026563665","https://openalex.org/W2028502361","https://openalex.org/W2037339322","https://openalex.org/W2060600855","https://openalex.org/W2078948823","https://openalex.org/W2089084692","https://openalex.org/W2095066810","https://openalex.org/W2119586900","https://openalex.org/W2154036516","https://openalex.org/W2162140339","https://openalex.org/W2162707187","https://openalex.org/W2170105701","https://openalex.org/W2507536774","https://openalex.org/W2755124766","https://openalex.org/W2802089023","https://openalex.org/W2808030638","https://openalex.org/W2887550150","https://openalex.org/W2899876501","https://openalex.org/W2904510888","https://openalex.org/W2914024845","https://openalex.org/W2988059933","https://openalex.org/W3029756541","https://openalex.org/W3119030790","https://openalex.org/W3132709478","https://openalex.org/W3209664507","https://openalex.org/W3217337816","https://openalex.org/W4212950351","https://openalex.org/W4226158523","https://openalex.org/W4228999517","https://openalex.org/W4292242922","https://openalex.org/W4380319625","https://openalex.org/W4392622738","https://openalex.org/W4395451793","https://openalex.org/W4396698955","https://openalex.org/W4399208023","https://openalex.org/W4400068072","https://openalex.org/W4401633397","https://openalex.org/W4408865756","https://openalex.org/W4411037540","https://openalex.org/W7139912058","https://openalex.org/W7158790410"],"related_works":[],"abstract_inverted_index":{"Abstract":[0],"Peptide":[1,24],"agonists":[2,151],"that":[3,107,198],"engage":[4],"multiple":[5],"G":[6],"protein-coupled":[7],"receptors":[8],"provide":[9],"a":[10,20,77,169,195],"framework":[11,220],"for":[12,190,221,230],"orchestrating":[13],"discrete":[14],"but":[15],"complementary":[16],"signaling":[17,51],"pathways":[18],"within":[19],"single":[21],"molecular":[22],"entity.":[23],"YY":[25],"(PYY)":[26],"is":[27,60,142],"an":[28,204],"endogenous":[29],"36-residue":[30],"multiagonist":[31],"of":[32,92,122],"the":[33,64,71,89,136,164,179,218],"neuropeptide":[34],"Y":[35],"receptor":[36,90,150,161,200],"(YR)":[37],"family.":[38],"Full-length":[39],"PYY(1\u201336)":[40,181,215],"activates":[41],"both":[42,117],"Y1R":[43,83,118],"and":[44,49,119,148,193,229],"Y2R,":[45],"coupling":[46],"Y1R-dependent":[47],"pancreatic":[48],"glucoregulatory":[50],"with":[52,80,159,209],"Y2R-dependent":[53],"satiety":[54],"pathways.":[55],"This":[56],"native":[57,124,223],"dual":[58,125],"agonism":[59,115,126],"rapidly":[61],"uncoupled":[62],"by":[63,130],"ubiquitous":[65],"dipeptidyl":[66],"peptidase-4":[67],"(DPP4),":[68],"which":[69],"removes":[70],"N-terminal":[72,138,166,187],"dipeptide":[73],"to":[74,110,145,173],"yield":[75],"PYY(3\u201336),":[76],"Y2R-selective":[78],"ligand":[79],"markedly":[81],"reduced":[82],"activity.":[84],"Thus,":[85],"DPP4":[86,111,175],"hydrolysis":[87],"alters":[88],"pharmacology":[91,225],"PYY":[93,105,157],"rather":[94],"than":[95],"merely":[96],"shortening":[97],"peptide":[98],"lifetime.":[99],"Here,":[100],"we":[101],"report":[102],"chemically":[103],"stabilized":[104],"analogues":[106,216],"are":[108],"refractory":[109],"while":[112,177,202],"retaining":[113],"potent":[114],"at":[116,135,163],"Y2R.":[120],"Preservation":[121],"this":[123],"was":[127],"not":[128],"achieved":[129],"introducing":[131],"2-aminoisobutyric":[132],"acid":[133],"(Aib)":[134],"penultimate":[137],"residue.":[139],"Although":[140],"Aib":[141],"widely":[143],"used":[144],"protect":[146],"GLP-1":[147],"GIP":[149],"from":[152],"DPP4,":[153],"it":[154],"results":[155],"in":[156,226],"derivatives":[158],"diminished":[160],"activity":[162,201],"Y1R.":[165],"alkylation":[167],"afforded":[168],"minimally":[170],"perturbative":[171],"strategy":[172],"block":[174],"recognition":[176],"maintaining":[178],"full-length":[180],"functional":[182],"pharmacophore.":[183],"Structure\u2013activity":[184],"studies":[185],"define":[186],"features":[188],"required":[189],"dual-receptor":[191],"potency":[192,206],"identify":[194],"lipidation":[196],"site":[197],"retains":[199],"producing":[203],"HSA-dependent":[205],"shift":[207],"consistent":[208],"albumin":[210],"association.":[211],"Together,":[212],"these":[213],"protease-stable":[214],"expand":[217],"chemical":[219],"preserving":[222],"multireceptor":[224],"DPP4-sensitive":[227],"peptides":[228],"engineering":[231],"long-acting":[232],"therapeutic":[233],"analogues.":[234]},"counts_by_year":[],"updated_date":"2026-11-12T12:28:57.059296","created_date":"2026-11-12T00:00:00"}