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

Result code in 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>

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

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

Name of the periodical

Journal of Peptide Science

ISSN

1075-2617

e-ISSN

1099-1387

Volume of the periodical

29

Issue of the periodical within the volume

7

Country of publishing house

GB - UNITED KINGDOM

Number of pages

9

Pages from-to

e3478

UT code for WoS article

000920623200001

EID of the result in the Scopus database

2-s2.0-85147221608