Modulation of the antagonistic properties of an insulin mimetic peptide by disulfide bridge modifications

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F23%3A00567614" target="_blank" >RIV/61388963:_____/23:00567614 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1002/psc.3478" target="_blank" >https://doi.org/10.1002/psc.3478</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/psc.3478" target="_blank" >10.1002/psc.3478</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Modulation of the antagonistic properties of an insulin mimetic peptide by disulfide bridge modifications

Popis výsledku v původním jazyce

Insulin is a peptide responsible for regulating the metabolic homeostasis of theorganism, it elicits its effects through binding to the transmembrane insulin receptor(IR). Insulin mimetics with agonistic or antagonistic effects toward the receptor arean exciting field of research and could find applications in treating diabetes ormalignant diseases. We prepared five variants of a previously reported 20-amino acidinsulin-mimicking peptide. These peptides differ from each other by the structure ofthe covalent bridge connecting positions 11 and 18. In addition to the peptide with a disulfide bridge, a derivative with a dicarba bridge and three derivatives with a1,2,3-triazole differing from each other by the presence of sulfur or oxygen in theirstaples were prepared. The strongest binding to IR was exhibited by the peptide with a disulfide bridge. All other derivatives only weakly bound to IR, and a relationshipbetween increasing bridge length and lower binding affinity can be inferred. Despite their nanomolar affinities, none of the prepared peptide mimetics was able to activate the insulin receptor even at high concentrations, but all mimetics were able to inhibit insulin-induced receptor activation. However, the receptor remained approximately 30% active even at the highest concentration of the agents, thus, the agents behave as partial antagonists. An interesting observation is that these mimetic peptides do not antagonize insulin action in proportion to their binding affinities. The compounds characterized in this study show that it is possible to modulate the functional properties of insulin receptor peptide ligands using disulfide mimetics.

Název v anglickém jazyce

Modulation of the antagonistic properties of an insulin mimetic peptide by disulfide bridge modifications

Popis výsledku anglicky

Insulin is a peptide responsible for regulating the metabolic homeostasis of theorganism, it elicits its effects through binding to the transmembrane insulin receptor(IR). Insulin mimetics with agonistic or antagonistic effects toward the receptor arean exciting field of research and could find applications in treating diabetes ormalignant diseases. We prepared five variants of a previously reported 20-amino acidinsulin-mimicking peptide. These peptides differ from each other by the structure ofthe covalent bridge connecting positions 11 and 18. In addition to the peptide with a disulfide bridge, a derivative with a dicarba bridge and three derivatives with a1,2,3-triazole differing from each other by the presence of sulfur or oxygen in theirstaples were prepared. The strongest binding to IR was exhibited by the peptide with a disulfide bridge. All other derivatives only weakly bound to IR, and a relationshipbetween increasing bridge length and lower binding affinity can be inferred. Despite their nanomolar affinities, none of the prepared peptide mimetics was able to activate the insulin receptor even at high concentrations, but all mimetics were able to inhibit insulin-induced receptor activation. However, the receptor remained approximately 30% active even at the highest concentration of the agents, thus, the agents behave as partial antagonists. An interesting observation is that these mimetic peptides do not antagonize insulin action in proportion to their binding affinities. The compounds characterized in this study show that it is possible to modulate the functional properties of insulin receptor peptide ligands using disulfide mimetics.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

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

7

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

9

Strana od-do

e3478

Kód UT WoS článku

000920623200001

EID výsledku v databázi Scopus

2-s2.0-85147221608