Strategies to improve the cholinesterase inhibitory activity of a novel peptide isolated from the skin secretions of Hysiboas pulchellus (Anura: Hylidae)

SIANO, ALVARO; ANDUJAR, SEBASTIAN; ENRIZ, RICARDO DANIEL; LAJMANOVICH, RAFAEL; TONARELLI, GEORGINA

Cordoba

Congreso; 3º Reunión Internacional de Ciencias Farmacéuticas, RICIFA 2014.; 2014

The butyrylcholinesterase (BChE) may represent an important therapeutic target for Alzheimer Disease (AD), and the search for new dual AChE (acetylcholinesterase) and BChE inhibitors is mandatory to find new alternative treatments for AD patients that do not respond to selective AChE inhibitors. P1-Hp-1971 (TKPTLLGLPLGAGPAAGPGKR) is a proline-glycine rich peptide which was identified in the skin secretions of Hypsiboas pulchellus. It was found that this peptide inhibited BChE and AChE enzymes (35% and 20% respectively at 400 µM). In this work, molecular docking calculations were carried out on BChE protein model (pdb-1P0M) to get better insights about the interaction peptide-enzyme, in order to delineate smaller bioactive analogs. According to these results five shorter sequences showed the highest in silico interactions, and were further synthesized by Fmoc (9-Fluorenylmethoxycarbonyl) chemistry.