Targeting the insulin receptor with hormone and peptide dimers

0564527 - ÚOCHB 2024 RIV GB eng J - Článek v odborném periodiku
Lin, Jingjing - Selicharová, Irena - Mitrová, Katarína - Fabre, Benjamin - Miriyala, Vijay Madhav - Lepšík, Martin - Jiráček, Jiří - Garre Hernández, María Soledad
Targeting the insulin receptor with hormone and peptide dimers.
Journal of Peptide Science. Roč. 29, č. 4 (2023), č. článku e3461. ISSN 1075-2617. E-ISSN 1099-1387
Grant CEP: GA MŠMT(CZ) EF16_019/0000729
Institucionální podpora: RVO:61388963
Klíčová slova: insulin * dimer * bioconjugate * agonism * antagonism * peptidomimetics * receptor * peptide hormone
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 2.1, rok: 2022
Způsob publikování: Omezený přístup
https://doi.org/10.1002/psc.3461

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. 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.
Trvalý link: https://hdl.handle.net/11104/0336187