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The dimeric character of the receptor for insulin evokes ideas about its activation or inhibition with peptide dimers that could either trigger or block the structural transition of the insulin receptor, leading to its activation. Herewith, we present the chemical engineering and biological characterization of several series of insulin dimers or dimers of specific peptides that should be able to bind receptors for insulin or insulin growth factor 1. The hormones or peptides in the dimers were interconnected with different linkers, consisting of triazole moieties and 3, 6, 8, 11, or 23 polyethylene glycol units. The prepared dimers were weaker in binding to insulin receptors than human insulin. However, some of the insulin dimers showed preferential binding specificity toward the isoform A of the insulin receptor, and the insulin dimers also stimulated the insulin receptor more strongly than would be consistent with their binding affinities. Our results suggest that designing insulin dimers may be a promising strategy for modulating the ability of the hormone to activate the receptor or to alter its specificity toward insulin receptor isoforms.<\/jats:p>","DOI":"10.1002\/psc.3461","type":"journal-article","created":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T03:19:31Z","timestamp":1667791171000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting the insulin receptor with hormone and peptide dimers"],"prefix":"10.1002","volume":"29","author":[{"given":"Jingjing","family":"Lin","sequence":"first","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences  Prague Czech Republic"},{"name":"Department of Biochemistry, Faculty of Science Charles University  Prague Czech 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