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Extending this learning, we hypothesised that a self-assembling lipidized peptide arginine vasopressin (AVP) receptor agonist, that had not been designed as a prodrug, could prove pharmacologically active and control urine production. The only approved AVP receptor agonist, desmopressin is indicated for the treatment of central diabetes insipidus (DI), bedwetting, haemophilia A and von Willebrand disease. Desmopressin is well tolerated by most patients, however adverse effects, such as hyponatraemia and water intoxication necessitate a strict fluid intake, thus motivating the search for alternative DI treatments. Selective V2 receptor agonism is required for anti-DI activity and we hypothesised that our new lipidized peptide (METx) would lead to selective AVP receptor agonism. METx was synthesised and characterised and then tested for activity against the V2, V1a and OT uterine receptors and not tested against the V1b receptor as METx was not expected to cross the blood brain barrier. METx was also tested <jats:italic>in vivo<\/jats:italic> in a healthy rat model. METx forms nanofibers and is a partial V2 receptor agonist (determined by measuring MDCK cell line cAMP accumulation), producing 57% of AVP\u2019s maximal activity (EC50\u2009=\u20092.7\u2009nM) and is not a V1a agonist up to a concentration of 1 \u03bcM (determined by measuring A7r5 cell line D-myo-inositol-1-phosphate accumulation). METx is a weak OT receptor antagonist, reducing the frequency of OT induced contractions (EC50\u2009=\u2009350\u2009nM) and increasing the OT EC50 from 0.081\u2009nM to 21\u2009nM at a concentration of 600\u2009nM. METx (41\u2009nM) had no effect on spontaneous uterine contractions and METx (100\u2009nM) had no effect on OT induced uterine contractions. Simulated binding studies show that binding avidity to the receptors follows the trend: V2\u2009&gt;\u2009OT\u2009&gt;\u2009V1a. On intravenous injection, a nanoparticle formulation of METx reduced urine production in a healthy rat model in a dose responsive manner, with 40\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup> METx resulting in no urine production over 4\u2009hours. The lipidized self-assembling peptide \u2013 METx - is a selective competitive V2 receptor agonist and an anti-diuretic.<\/jats:p>","DOI":"10.1038\/s41598-020-64070-9","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T10:03:28Z","timestamp":1588154608000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Self-Assembling Lipidic Peptide and Selective Partial V2 Receptor Agonist Inhibits Urine Production"],"prefix":"10.1038","volume":"10","author":[{"given":"Sunish","family":"Patel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella Bavuso","family":"Volpe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar","family":"Awwad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas G.","family":"Sch\u00e4tzlein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shozeb","family":"Haider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boqian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ijeoma F.","family":"Uchegbu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,29]]},"reference":[{"key":"64070_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/bip.21328","volume":"94","author":"H Cui","year":"2010","unstructured":"Cui, H., Webber, M. 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