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Inhibition of the PlexinB1-Semaphorin4D interaction on osteoblasts has been shown to be a potential target for developing osteoanabolic modalities. Here, using a novel affinity maturation approach for cyclic peptides, we were able to develop cyclic peptide that tightly binds human and mouse PlexinB1 and inhibits its interaction with Semaphorin4D. Chemical dimerization of this peptide resulted in further increases in activity and demonstrated complete rescue of bone loss in an osteoporosis mouse model.<\/jats:p>","DOI":"10.1073\/pnas.2012266117","type":"journal-article","created":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T21:13:09Z","timestamp":1606165989000},"page":"31070-31077","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":28,"title":["Development of cyclic peptides with potent in vivo osteogenic activity through RaPID-based affinity maturation"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9175-0947","authenticated-orcid":false,"given":"Nasir K.","family":"Bashiruddin","sequence":"first","affiliation":[{"name":"Department of Chemistry, Graduate School of Science, The University of Tokyo, Tokyo 113-0033 Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6576-1466","authenticated-orcid":false,"given":"Mikihito","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8549, Japan;"},{"name":"Japan Agency for Medical Research and Development, Precursory Research for Innovative Medical Care, Tokyo 113-8549, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanobu","family":"Nagano","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Graduate School of Science, The University of Tokyo, Tokyo 113-0033 Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1316-4867","authenticated-orcid":false,"given":"Yan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Graduate School of Science, The University of Tokyo, Tokyo 113-0033 Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Matsunaga","sequence":"additional","affiliation":[{"name":"Laboratory of Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Suita-shi, Osaka 565-0871, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1219-475X","authenticated-orcid":false,"given":"Junichi","family":"Takagi","sequence":"additional","affiliation":[{"name":"Laboratory of Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Suita-shi, Osaka 565-0871, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6779-8617","authenticated-orcid":false,"given":"Tomoki","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8549, Japan;"},{"name":"Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology, Tokyo 113-8549, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5298-9186","authenticated-orcid":false,"given":"Hiroaki","family":"Suga","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Graduate School of Science, The University of Tokyo, Tokyo 113-0033 Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,11,23]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32112-3"},{"key":"e_1_3_4_2_2","first-page":"92","article-title":"Osteoporosis: A review of treatment options","volume":"43","author":"Tu K. 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