{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:48:03Z","timestamp":1790430483624,"version":"4.1.0"},"reference-count":61,"publisher":"National Academy of Sciences","issue":"49","license":[{"start":{"date-parts":[[2019,5,15]],"date-time":"2019-05-15T00:00:00Z","timestamp":1557878400000},"content-version":"vor","delay-in-days":181,"URL":"http:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01 GM05641"],"award-info":[{"award-number":["R01 GM05641"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["P01 DK11794"],"award-info":[{"award-number":["P01 DK11794"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["P30 AR066261"],"award-info":[{"award-number":["P30 AR066261"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32 GM008349"],"award-info":[{"award-number":["T32 GM008349"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2018,12,4]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>G-protein-coupled receptors (GPCRs) mediate diverse physiological processes and are targets of many therapeutic agents. GPCR subfamilies comprise related receptors that can be activated by the same or similar agonists but manifest distinct functions. Subtype-selective agonists are valuable as tools for fundamental research and as drug candidates with minimal side effects. It is challenging, however, to develop agonists with differentiated activities at structurally related receptors. We started from a human parathyroid hormone fragment that is used to treat osteoporosis, and developed subtype-selective variants by modifying the peptide backbone while maintaining the natural side chains. Our findings suggest that backbone modification, which has received little prior attention in terms of tailoring polypeptide hormone specificity, may represent a general source of receptor-selective agonists.<\/jats:p>","DOI":"10.1073\/pnas.1815294115","type":"journal-article","created":{"date-parts":[[2018,11,15]],"date-time":"2018-11-15T17:26:47Z","timestamp":1542302807000},"page":"12383-12388","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":33,"title":["Receptor selectivity from minimal backbone modification of a polypeptide agonist"],"prefix":"10.1073","volume":"115","author":[{"given":"Shi","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Wisconsin\u2013Madison, Madison, WI 53706;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross W.","family":"Cheloha","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Wisconsin\u2013Madison, Madison, WI 53706;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospital, Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Gardella","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospital, Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5617-0058","authenticated-orcid":false,"given":"Samuel H.","family":"Gellman","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Wisconsin\u2013Madison, Madison, WI 53706;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2018,11,15]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2001-2-12-reviews3013"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2011.170"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.114.009464"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2010.08.004"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0419"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/14724"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2009.02.012"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.33.19888"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.137.10.8828480"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01676.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M211945200"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002325200"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(84)91449-9"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm101425m"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/cn5000953"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200390078"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm4008505"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.110.164301"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/psc.1175"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2003.18.11.1932"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2004.pto940602.x"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0801027105"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-127-1-83"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.134.2.8299582"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.7.2732"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503942102"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2014.10.003"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2013.05.011"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2017.06.052"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2920"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja302469a"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb500888q"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-394292-0.00019-9"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2016.06.014"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2017.03.018"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0801135105"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja8099294"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja207148m"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1039\/C6CC00273K"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/hlca.200890190"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja071203r"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.8b05162"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201806909"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb200248h"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2014-1129"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b00876"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M009395200"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)61507-3"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature22800"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature22394"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature22327"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2017.10.003"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.46.28861"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2015-1726"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.206"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1589"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)47429-2"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2015.139"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.07.004"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2006.12.002"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-123-5-2597"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1815294115","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1815294115","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T03:15:38Z","timestamp":1649819738000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1815294115"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,15]]},"references-count":61,"journal-issue":{"issue":"49","published-print":{"date-parts":[[2018,12,4]]}},"alternative-id":["10.1073\/pnas.1815294115"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1815294115","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,15]]},"assertion":[{"value":"2018-11-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}