Search for lipidized PrRP analogs with strong anorexigenic effect: In vitro and in vivo studies

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F23%3A00570639" target="_blank" >RIV/61388963:_____/23:00570639 - isvavai.cz</a>

Alternative codes found

RIV/67985823:_____/23:00571848 RIV/60461373:22340/23:43925121 RIV/00216208:11110/23:10465222

Result on the web

<a href="https://doi.org/10.1016/j.npep.2022.102319" target="_blank" >https://doi.org/10.1016/j.npep.2022.102319</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.npep.2022.102319" target="_blank" >10.1016/j.npep.2022.102319</a>

Result language

angličtina

Original language name

Search for lipidized PrRP analogs with strong anorexigenic effect: In vitro and in vivo studies

Original language description

Prolactin-releasing peptide (PrRP) is an anorexigenic neuropeptide that attenuates food intake and increases energy expenditure. We designed three series of new lipidized PrRP31 analogs of different lengths of fatty acids attached at amino acids 1 or 11 directly or via linkers, part of them acetylated at the N-terminus and/or modified with dichlorophenylalanine (PheCl2) at the C-terminus. We tested their affinity for and activation of signaling pathways relevant to receptors GPR10, NPFF-R2, and NPFF-R1, effect on food intake in fasted or freely fed mice and rats, and stability in rat plasma. We aimed to select a strong dual GPR10/NPFF-R2 agonist whose affinity for NPFF-1 was not enhanced. The selected potent analog was then tested for body weight-lowering potency after chronic administration in mice with diet-induced obesity. PrRP31 analogs lipidized by monocarboxylic fatty acids showed strong dual affinity for both GPR10 and NPFF-R2 and activated MAPK/ERK1/2, Akt and CREB in cells overexpressing GPR10 and NPFF-R2. The selected analog stabilized at N- and C-termini and palmitoylated through the TTDS linker to Lys11 is a powerful dual agonist GPR10/NPFF-R2 at not enhanced affinity for NPFF-R1. It showed strong anti-obesity properties in mice with diet-induced obesity and became a potential compound for further studies.

Czech name

—

Czech description

—

Type

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

CEP classification

—

OECD FORD branch

30105 - Physiology (including cytology)

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

Neuropeptides

ISSN

0143-4179

e-ISSN

1532-2785

Volume of the periodical

98

Issue of the periodical within the volume

April

Country of publishing house

GB - UNITED KINGDOM

Number of pages

12

Pages from-to

102319

UT code for WoS article

000963271700001

EID of the result in the Scopus database

2-s2.0-85149800491