Probing Tripodal Peptide Scaffolds as Insulin and IGF-1 Receptor Ligands

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F18%3A00495744" target="_blank" >RIV/61388963:_____/18:00495744 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1002/ejoc.201800606" target="_blank" >http://dx.doi.org/10.1002/ejoc.201800606</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/ejoc.201800606" target="_blank" >10.1002/ejoc.201800606</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Probing Tripodal Peptide Scaffolds as Insulin and IGF-1 Receptor Ligands

Popis výsledku v původním jazyce

Non-natural compounds mimicking the actions of proteins and large peptides can find a plethora of applications in modulating protein-protein interactions. In this study, the biological properties of three new tripodal and trifunctional scaffolds designed for the solid-phase synthesis of three different peptides on the same scaffold were tested. Using model peptide sequences derived from receptor-binding epitopes from insulin or peptides derived from previously developed insulin mimetics, the quality of scaffold-derived compounds were probed as binders of the insulin and IGF-1 receptors and as activators of the insulin receptor. Two compounds were identified that could bind insulin receptors with low micromolar affinities. It was found that factors influencing the activities of scaffold-based compounds are complex and that the properties of compounds are due to specific peptide sequences placed on specific arms of the scaffolds. This opens up new avenues for combinatorial libraries of scaffold-based compounds, which could provide new activators or inhibitors of both receptors. The potential of the scaffold-based compounds is further underlined by a substantially higher metabolic stability of scaffold-linked peptides compared to peptides alone.

Název v anglickém jazyce

Probing Tripodal Peptide Scaffolds as Insulin and IGF-1 Receptor Ligands

Popis výsledku anglicky

Non-natural compounds mimicking the actions of proteins and large peptides can find a plethora of applications in modulating protein-protein interactions. In this study, the biological properties of three new tripodal and trifunctional scaffolds designed for the solid-phase synthesis of three different peptides on the same scaffold were tested. Using model peptide sequences derived from receptor-binding epitopes from insulin or peptides derived from previously developed insulin mimetics, the quality of scaffold-derived compounds were probed as binders of the insulin and IGF-1 receptors and as activators of the insulin receptor. Two compounds were identified that could bind insulin receptors with low micromolar affinities. It was found that factors influencing the activities of scaffold-based compounds are complex and that the properties of compounds are due to specific peptide sequences placed on specific arms of the scaffolds. This opens up new avenues for combinatorial libraries of scaffold-based compounds, which could provide new activators or inhibitors of both receptors. The potential of the scaffold-based compounds is further underlined by a substantially higher metabolic stability of scaffold-linked peptides compared to peptides alone.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

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

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

European Journal of Organic Chemistry

ISSN

1434-193X

e-ISSN

—

Svazek periodika

2018

Číslo periodika v rámci svazku

37

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

9

Strana od-do

5193-5201

Kód UT WoS článku

000446662900013

EID výsledku v databázi Scopus

2-s2.0-85050937124