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

SIANO, ALVARO; SANCHIS, IVAN; SPINELLI, ROQUE; ENRIZ, RICARDO DANIEL; TONARELLI, GEORGINA

Rosario

Congreso; 4º Reunión Internacional de Ciencias Farmacéuticas; 2016

The butyrylcholinesterase (BChE) and acetilcholinesterse (AChE) 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). Five shorter sequences were further synthesized by Fmoc (9-Fluorenylmethoxycarbonyl) chemistry. The hemolytic and cholinesterase inhibitory activity were determined by experimental optimized protocols and showed that analogs 7-21 and 5-21 presented the highest inhibitory effect against both enzymes (over 45% at 100 µM) while the shortest peptides (8-15 and 11-16) showed similar inhibitory activity like P1-Hp-1971.