Targeting the insulin receptor with hormone and peptide dimers

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15640%2F22%3A73618689" target="_blank" >RIV/61989592:15640/22:73618689 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388963:_____/23:00564527 RIV/00216208:11310/23:10464279

Výsledek na webu

<a href="https://onlinelibrary.wiley.com/doi/10.1002/psc.3461" target="_blank" >https://onlinelibrary.wiley.com/doi/10.1002/psc.3461</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/psc.3461" target="_blank" >10.1002/psc.3461</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Targeting the insulin receptor with hormone and peptide dimers

Popis výsledku v původním jazyce

Insulin is a key hormone involved in the regulation of overall energetic homeostasis of the organism. 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.

Název v anglickém jazyce

Targeting the insulin receptor with hormone and peptide dimers

Popis výsledku anglicky

Insulin is a key hormone involved in the regulation of overall energetic homeostasis of the organism. 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

21002 - Nano-processes (applications on nano-scale); (biomaterials to be 2.9)

Projekt

<a href="/cs/project/EF16_019%2F0000729" target="_blank" >EF16_019/0000729: Chemická biologie pro vývoj nových terapií</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

JOURNAL OF PEPTIDE SCIENCE

ISSN

1075-2617

e-ISSN

1099-1387

Svazek periodika

29

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

9

Strana od-do

"nečíslováno"

Kód UT WoS článku

000883179300001

EID výsledku v databázi Scopus

2-s2.0-85142158035