Proliferative and signaling properties of IGF and insulin analogs with promiscuous binding to both insulin and insulin-like growth factor 1 receptors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00641785" target="_blank" >RIV/61388963:_____/25:00641785 - isvavai.cz</a>

Výsledek na webu

<a href="https://hdl.handle.net/11104/0371818" target="_blank" >https://hdl.handle.net/11104/0371818</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Proliferative and signaling properties of IGF and insulin analogs with promiscuous binding to both insulin and insulin-like growth factor 1 receptors

Popis výsledku v původním jazyce

Insulin and insulin-like growth factor 1 (IGF-1) are closely related hormones involved in the regulation of metabolism and growth. They elicit their functions through activation of tyrosine kinase-type receptors: insulin receptors (IR-A and IR-B) and IGF-1 receptor (IGF-1R). Despite similarity in primary and threedimensional structures, insulin and IGF-1 bind the noncognate receptor with substantially reduced affinity. In this study we focused on closer characterization of our previously prepared analogs with promiscuous binding to both the IR and IGR-1R and their potential impact on cells of neurological origin. We employed our analogs [His49]-IGF-1 and [His48]-IGF-2 with increased binding to IR-A compared to the wild-type hormones. Of special relevance, we prepared [GluB10, D-HisB24, GlyB31, TyrB32]-insulin, which binds all three receptors with unusually high affinity: 209 or 950 % binding affinity to IR-A, respectively to IR-B, relative to insulin and, remarkably, 79 % binding affinity to IGF-1R relative to IGF-1. We show the increased proliferative activity of the promiscuous analogs together with potentiation of the insulin/IGF-1 signaling pathway in the cells of neuronal origin. We suggest that the new super-potent insulin analog might be an ideal candidate for use where the growth potential of both insulin and IGF-1 is needed, which may be, for example, media for stimulating cell growth and differentiation, and where a single derivative could replace the action of two native hormones with greater efficiency and at lower cost. We developed and studied new insulin/IGF-1 dual agonist that binds insulin and IGF-1 receptors with very high affinity and stimulates neuronal cell growth more effectively than native hormones. Such molecules may replace both hormones in cell culture, offering greater efficiency and lower cost.

Název v anglickém jazyce

Proliferative and signaling properties of IGF and insulin analogs with promiscuous binding to both insulin and insulin-like growth factor 1 receptors

Popis výsledku anglicky

Insulin and insulin-like growth factor 1 (IGF-1) are closely related hormones involved in the regulation of metabolism and growth. They elicit their functions through activation of tyrosine kinase-type receptors: insulin receptors (IR-A and IR-B) and IGF-1 receptor (IGF-1R). Despite similarity in primary and threedimensional structures, insulin and IGF-1 bind the noncognate receptor with substantially reduced affinity. In this study we focused on closer characterization of our previously prepared analogs with promiscuous binding to both the IR and IGR-1R and their potential impact on cells of neurological origin. We employed our analogs [His49]-IGF-1 and [His48]-IGF-2 with increased binding to IR-A compared to the wild-type hormones. Of special relevance, we prepared [GluB10, D-HisB24, GlyB31, TyrB32]-insulin, which binds all three receptors with unusually high affinity: 209 or 950 % binding affinity to IR-A, respectively to IR-B, relative to insulin and, remarkably, 79 % binding affinity to IGF-1R relative to IGF-1. We show the increased proliferative activity of the promiscuous analogs together with potentiation of the insulin/IGF-1 signaling pathway in the cells of neuronal origin. We suggest that the new super-potent insulin analog might be an ideal candidate for use where the growth potential of both insulin and IGF-1 is needed, which may be, for example, media for stimulating cell growth and differentiation, and where a single derivative could replace the action of two native hormones with greater efficiency and at lower cost. We developed and studied new insulin/IGF-1 dual agonist that binds insulin and IGF-1 receptors with very high affinity and stimulates neuronal cell growth more effectively than native hormones. Such molecules may replace both hormones in cell culture, offering greater efficiency and lower cost.

Druh

O - Ostatní výsledky

CEP obor

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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

2025

Kód důvěrnosti údajů

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