{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:05:25Z","timestamp":1792782325212,"version":"4.5.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2016,7,18]],"date-time":"2016-07-18T00:00:00Z","timestamp":1468800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"NIH","award":["DK11794"],"award-info":[{"award-number":["DK11794"]}]},{"name":"NIH","award":["AR066261"],"award-info":[{"award-number":["AR066261"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,1,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>\u2003<\/jats:title>\n                    <jats:p>Polyethylene glycol (PEG) addition can prolong the pharmacokinetic and pharmacodynamic actions of a bioactive peptide in vivo, in part by impeding rates of glomerular filtration. For parathyroid hormone (PTH) peptides, pegylation could help in exploring the actions of the hormone in the kidney; e.g., in dissecting the relative roles that filtered versus blood-borne PTH play in regulating phosphate transport. It could also lead to potential alternate forms of treatment for hypoparathyroidism. We thus synthesized the fluorescent pegylated PTH derivative [Lys13(tetramethylrhodamine {TMR}), Cys35(PEG-20,000 Da)]PTH(1-35) (PEG-PTHTMR) and its non-pegylated counterpart [Lys13(TMR), Cys35]PTH(1-35) (PTHTMR) and assessed their properties in cells and in mice. In PTHR1-expressing HEK-293 cells, PEG-PTHTMR and PTHTMR exhibited similar potencies for inducing cAMP signaling, whereas when injected into mice, the pegylated analog persisted much longer in the circulation (&amp;gt;24 hours versus\u2009\u223c\u20091 hour) and induced markedly more prolonged calcemic and phosphaturic responses than did the non-pegylated control. Fluorescence microscopy analysis of kidney sections obtained from the injected mice revealed much less PEG-PTHTMR than PTHTMR on the luminal brush-border surfaces of renal proximal tubule cells (PTCs), on which PTH regulates phosphate transporter function, whereas immunostained phosphorylated PKA substrate, a marker of cAMP signaling, was increased to similar extents for the two ligands and for each, was localized to the basolateral portion of the PTCs. Pegylation of a bioactive PTH peptide thus led to prolonged pharmacokinetic\/pharmacodynamic properties in vivo, as well as to new in vivo data that support a prominent role for PTH action at basolateral surfaces of renal proximal tubule cells. \u00a9 2016 American Society for Bone and Mineral Research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbmr.2917","type":"journal-article","created":{"date-parts":[[2016,7,18]],"date-time":"2016-07-18T10:37:05Z","timestamp":1468838225000},"page":"86-98","source":"Crossref","is-referenced-by-count":31,"title":["Prolonged Pharmacokinetic and Pharmacodynamic Actions of a Pegylated Parathyroid Hormone (1-34) Peptide Fragment"],"prefix":"10.1093","volume":"32","author":[{"given":"Jun","family":"Guo","sequence":"first","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospitaland Harvard Medical SchoolBostonMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok","family":"Khatri","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospitaland Harvard Medical SchoolBostonMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Maeda","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospitaland Harvard Medical SchoolBostonMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"John T","family":"Potts","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospitaland Harvard Medical SchoolBostonMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"J\u00fcppner","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospitaland Harvard Medical SchoolBostonMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J","family":"Gardella","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospitaland Harvard Medical SchoolBostonMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,7,18]]},"reference":[{"issue":"1","key":"2024021014264519000_jbmr2917-bib-0001","doi-asserted-by":"crossref","first-page":"8","DOI":"10.11005\/jbm.2014.21.1.8","article-title":"Bone biology and anabolic therapies for bone: current status and future prospects","volume":"21","author":"Martin","year":"2014","journal-title":"J Bone Metab"},{"issue":"2","key":"2024021014264519000_jbmr2917-bib-0002","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s11154-015-9318-z","article-title":"The PTH-vitamin D-FGF23 axis","volume":"16","author":"Blau","year":"2015","journal-title":"Rev Endocr Metab 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