Ustav Organicke Chemie a Biochemie Akademie Ved Cr, V.v.i.

Ustav Organicke Chemie a Biochemie Av Cr, V.v.i.

Fyziologicky Ustav Akademie Ved Cr, V.v.i.

Fyziologicky Ustav Akademie Ved Ceske Republiky, V.v.i.

Lenka Maletinska

Blanka Zelezna

Jaroslav Kunes

Miroslava Blechova

Andrea Popelova

Barbora Mikulaskova

Stepan Strnad

Andrea Spolcova

Veronika Prazienkova

Veronika Nagelova

Lipidated neuropeptides PrRP31, PrRP20, containing C14 to C16 fatty acid, and their analogs, wherein a sequence of IRPVGRF-NHat the C-terminus is variable in the site of isoleucine, valine and phenylalanine; said fatty acid is bound in position 1 or 11 for PrRP31 or its analog and in position 1 or 7 for PrRP20 or its analog; the bond comprises an amide bond between an amino acid having at least one free NHgroup and a carboxylic group of the fatty acid and alternatively includes also a binding through arm X, which is a hydrophilic linker selected from a group comprising &#x3b2;-alanine, &#x3b3;-aminobutyric acid or &#x3b3;-glutamic acid; for use in the treatment and prevention of diseases, which are Alzheimer's disease (AD), Parkinson's disease (PD), cognitive impairment no dementia (CIND), brain trauma, and neurodegenerative changes and disorders.

Lipidated peptides as neuroprotective agents

Lipidated analogs of prolactin-releasing peptides (PrRP) and their use in controlling and lowering blood glucose in mammals is disclosed. Useful compounds included lipidated analogs of PrRP20 and PrRP31. Pharmacological effects are demonstrated both in vitro and in vivo. Peripheral administration of the lipidated peptides towers blood glucose levels. These treatments are applicable for treating impaired glucose tolerance (IGT), and glucose intolerance condition. The disclosed compounds have application in treating medical conditions including diabetes, pre-diabetes, eating disorders, and obesity.

Lipidated peptides for lowering blood glucose

Lipidated peptides, analogs of both forms of the prolactin-releasing peptide, PrRP31 and PrRP20, represent anorexigenic compounds that lower food intake and function in the brain after peripheral administration. The analogs PrRP31 and PrRP20 lipidated at the N-terminus by myristic or palmitic acids bind with high affinity to the endogenous receptor GPR10 in the rat pituitary cell line RC-4B/C and CHO cell line with transfected human receptor. These lipidated peptides also significantly decrease, in a dose-dependent manner, the food intake in fasted mice and have similar effects in comparable doses as centrally administered natural PrRP31, these effects are, however, stronger and longer lasting. Lipidation of an effective anorexigenic neuropeptide PrRP induces a central effect after peripheral administration and thus makes the lipidated analogs of PrRP a promising anti-obesity drug.

Lipidated peptides as anti-obesity agents

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Prague, Czechia

Lenka Maletinska