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Search for lipidized PrRP analogs with strong anorexigenic effect: In vitro and in vivo studies
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SYSNO ASEP 0571848 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Search for lipidized PrRP analogs with strong anorexigenic effect: In vitro and in vivo studies Tvůrce(i) Strnadová, V. (CZ)
Karnošová, A. (CZ)
Blechová, M. (CZ)
Neprašová, B. (CZ)
Holá, L. (CZ)
Němcová, A. (CZ)
Myšková, A. (CZ)
Sýkora, D. (CZ)
Železná, B. (CZ)
Kuneš, Jaroslav (FGU-C) RID, ORCID
Maletínská, L. (CZ)Číslo článku 102319 Zdroj.dok. Neuropeptides. - : Elsevier - ISSN 0143-4179
Roč. 98, April (2023)Poč.str. 12 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova prolactin-releasing peptide ; lipidization ; GPR10 ; NPFF-R2 ; NPFF-R1 ; ERK ; Akt activation ; stability ; food intake Obor OECD Physiology (including cytology) CEP GA21-03691S GA ČR - Grantová agentura ČR LX22NPO5104 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora FGU-C - RVO:67985823 UT WOS 000963271700001 EID SCOPUS 85149800491 DOI 10.1016/j.npep.2022.102319 Anotace 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. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2024 Elektronická adresa https://doi.org/10.1016/j.npep.2022.102319
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