Antiamnesic properties of analogs and mimetics of the tripeptide human urocortin 3.
Amnesia is a deficit in memory caused by brain damage, disease, or trauma. Until now, there are no successful medications on the drug market available to treat amnesia. Short analogs and mimetics of human urocortin 3 (Ucn 3) tripeptide were synthetized and tested for their action against amnesia induced by eletroconvulsion in mice. Among the 16 investigated derivatives of Ucn 3 tripeptide, eight compounds displayed antiamnesic effect. Our results proved that the configuration of chiral center of glutamine does not affect the antiamnesic properties. Alkyl amide or isoleucyl amide at the C-terminus may lead to antiamnesic compounds. As concerned the N-terminus, acetyl, Boc, and alkyl ureido moieties were found among the active analogs, but the free amino function at the N-terminus usually led to an inactive derivatives. These observations may lead to the design and synthesis of small peptidomimetics and amino acid derivatives as antiamnesic drug candidates, although the elucidation of the mechanism of the action requires further investigations.
Department of Pathophysiology, University of Szeged, Semmelweis u. 1, Szeged, 6725, Hungary.|MTA-SZTE Neuroscience Research Group of the Hungarian Academy of Sciences, University of Szeged, Semmelweis u. 1, Szeged, 6725, Hungary.
Gyula
G
Telegdy
Department of Medical Chemistry, University of Szeged, Dóm tér 8, Szeged, 6720, Hungary.
Anita Kármen
AK
Kovács
Department of Medical Chemistry, University of Szeged, Dóm tér 8, Szeged, 6720, Hungary.
Kinga
K
Rákosi
Department of Medical Chemistry, University of Szeged, Dóm tér 8, Szeged, 6720, Hungary.
Márta
M
Zarándi
Department of Medical Chemistry, University of Szeged, Dóm tér 8, Szeged, 6720, Hungary. toth.gabor@med.u-szeged.hu.
Gábor K
GK
Tóth
D000647:Amnesia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000737:chemistry*; D005260:Female; D006801:Humans; D051379:Mice; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D057786:Peptidomimetics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D054832:Urocortins / Q000737:chemistry*
D009842:Oligopeptides; D057786:Peptidomimetics; C426704:UCN3 protein, human; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone
Antiamnesic effect; Passive avoidance learning; Peptidomimetics; Urocortin 3 fragments