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Acetylcholinesterase inhibitory activity of a naturally occurring peptide isolated from Boana pulchella (Anura: Hylidae) and its analogs


Alzheimer’s disease (AD), the most common form of dementia, is a growing problem worldwide, with 10 million incident cases registered every year. The complex etiology of AD has not been clarified yet and represents an active research topic. In this work, we studied the inhibitory properties of Hp-1935, a natural peptide extracted from the skin secretions of an Argentinian frog (Boana pulchella). It was initially isolated as an antimicrobial peptide by our group, but we later discovered its anti-AChE action. Since not many peptides with this activity have been reported, we focused on defining the basis of its inhibitory mechanism against acetylcholinesterase (AChE) and on finding the primary portion for the inhibitory activity in its sequence, through the combination of an experimental strategy of design and synthesis with molecular dynamics simulations. We also tested its cytotoxicity. We found that Hp-1935 is an interesting sequence for the development of new AChE inhibitors. This peptide is a peripheral anionic site inhibitor with an inhibitory activity that collocates it between the most potent natural amino acids peptides against AChE reported. We also demonstrate that its inhibitory activity is concentrated on the central part of the sequence.

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The work was supported by grants from the Universidad Nacional del Litoral (CAI + D Research Programs (PJ50020150100044LI) and Agencia Nacional de Promoción Científica y Tecnológica (PICT-2017-0035)

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Correspondence to Alvaro Siano.

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The authors declare that there is no conflict of interest among all authors of this manuscript, and no patients or animals were involved in this research.

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Sanchis, I., Spinelli, R., Aschemacher, N. et al. Acetylcholinesterase inhibitory activity of a naturally occurring peptide isolated from Boana pulchella (Anura: Hylidae) and its analogs. Amino Acids 52, 387–396 (2020).

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  • Peptides
  • Synthesis
  • Cholinesterase inhibitors
  • Alzheimer’s disease