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To overcome the drawback of kisspeptin short half-life we designed kisspeptin analogs combining original modifications, triazole peptidomimetic and albumin binding motif, to reduce proteolytic degradation and to slow down renal clearance, respectively. These analogs showed improved <jats:italic>in vitro<\/jats:italic> potency and dramatically enhanced pharmacodynamics. When injected intramuscularly into ewes (15\u2009nmol\/ewe) primed with a progestogen, the best analog (compound <jats:bold>6<\/jats:bold>, <jats:bold>C6<\/jats:bold>) induced synchronized ovulations in both breeding and non-breeding seasons. Ovulations were fertile as demonstrated by the delivery of lambs at term. <jats:bold>C6<\/jats:bold> was also fully active in both female and male mice but was completely inactive in KiSS1R KO mice. Electrophysiological recordings of GnRH neurons from brain slices of GnRH-GFP mice indicated that <jats:bold>C6<\/jats:bold> exerted a direct excitatory action on GnRH neurons. Finally, in prepubertal female mice daily injections (0.3\u2009nmol\/mouse) for five days significantly advanced puberty. <jats:bold>C6<\/jats:bold> ability to trigger ovulation and advance puberty demonstrates that kisspeptin analogs may find application in the management of livestock reproduction and opens new possibilities for the treatment of reproductive disorders in humans.<\/jats:p>","DOI":"10.1038\/srep26908","type":"journal-article","created":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T09:43:39Z","timestamp":1464774219000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["A synthetic kisspeptin analog that triggers ovulation and advances puberty"],"prefix":"10.1038","volume":"6","author":[{"given":"C.","family":"Decourt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Robert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Anger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Galibert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.-B.","family":"Madinier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Dardente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Lomet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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