Pharmacological characterization of lipidized analogs of prolactin-releasing peptide with a modified C-terminal aromatic ring

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F16%3A00459379" target="_blank" >RIV/61388963:_____/16:00459379 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.jpp.krakow.pl/journal/archive/02_16/articles/11_article.html" target="_blank" >http://www.jpp.krakow.pl/journal/archive/02_16/articles/11_article.html</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Pharmacological characterization of lipidized analogs of prolactin-releasing peptide with a modified C-terminal aromatic ring

Popis výsledku v původním jazyce

Prolactin-releasing peptide (PrRP) is an anorexigenic neuropeptide expressed in the brain where it regulates food intake and energy expenditure. The C-terminal Arg-Phe-NH2 of PrRP is crucial for its biological activity. In our previous study, we showed that PrRP analogs myristoylated or palmitoylated at the N-terminus seem to cross the blood-brain barrier and lower food intake following peripheral administration. In this study, myristoylated and palmitoylated PrRP31 analogs with a modified C-terminal Phe were designed and tested. Lipidized analogs containing Phe31 replaced by aromatic noncoded amino acids or tyrosine revealed high binding affinity to rat pituitary RC-4B/C cells with endogenous PrRP and neuropeptide FF 2 receptors and to CHO-K1 cells overexpressing either PrRP or neuropeptide FF 2 receptors. The analogs also showed strong agonistic properties at the GPR10 receptor using the beta-lactamase reporter gene assay. Moreover, lipidized PrRP analogs, especially those that were palmitoylated, demonstrated strong and long-lasting anorexigenic effects in fasted mice after subcutaneous administration. The most efficient PrRP31 analogs with PheCl(2)(31), either palmitoylated or myristoylated at the N-terminus, are promising candidates for the study of food disorders, possibly for anti-obesity treatment. Despite the therapeutic potential in targeting central GPR10, the endogenous ligand PrRP cannot cross the blood-brain barrier. Understanding biological activity and transport of novel structural analogs of PrRP with a potential central anorexigenic effect is of key therapeutic significance.

Název v anglickém jazyce

Pharmacological characterization of lipidized analogs of prolactin-releasing peptide with a modified C-terminal aromatic ring

Popis výsledku anglicky

Prolactin-releasing peptide (PrRP) is an anorexigenic neuropeptide expressed in the brain where it regulates food intake and energy expenditure. The C-terminal Arg-Phe-NH2 of PrRP is crucial for its biological activity. In our previous study, we showed that PrRP analogs myristoylated or palmitoylated at the N-terminus seem to cross the blood-brain barrier and lower food intake following peripheral administration. In this study, myristoylated and palmitoylated PrRP31 analogs with a modified C-terminal Phe were designed and tested. Lipidized analogs containing Phe31 replaced by aromatic noncoded amino acids or tyrosine revealed high binding affinity to rat pituitary RC-4B/C cells with endogenous PrRP and neuropeptide FF 2 receptors and to CHO-K1 cells overexpressing either PrRP or neuropeptide FF 2 receptors. The analogs also showed strong agonistic properties at the GPR10 receptor using the beta-lactamase reporter gene assay. Moreover, lipidized PrRP analogs, especially those that were palmitoylated, demonstrated strong and long-lasting anorexigenic effects in fasted mice after subcutaneous administration. The most efficient PrRP31 analogs with PheCl(2)(31), either palmitoylated or myristoylated at the N-terminus, are promising candidates for the study of food disorders, possibly for anti-obesity treatment. Despite the therapeutic potential in targeting central GPR10, the endogenous ligand PrRP cannot cross the blood-brain barrier. Understanding biological activity and transport of novel structural analogs of PrRP with a potential central anorexigenic effect is of key therapeutic significance.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FB - Endokrinologie, diabetologie, metabolismus, výživa

OECD FORD obor

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Projekt

<a href="/cs/project/GA15-08679S" target="_blank" >GA15-08679S: Vliv stabilních analogů peptidu uvolňujícího prolaktin na obezitu a hypertenzi v experimentálních modelech</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

Journal of Physiology and Pharmacology

ISSN

0867-5910

e-ISSN

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Svazek periodika

67

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

PL - Polská republika

Počet stran výsledku

8

Strana od-do

121-128

Kód UT WoS článku

000373380100011

EID výsledku v databázi Scopus

2-s2.0-84961603835