Rational design and synthesis of modified natural peptides from Boana pulchella (anura) as acetylcholinesterase inhibitors and antioxidants

Sanchís, Ivan; Spinelli, Roque; Aschemacher, Nicolas; Siano, Álvaro Sebastián

doi:10.1007/s00726-021-03096-3

Cited by 6 publications

(13 citation statements)

References 62 publications

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“…Remarkably, W3 peptide also showed significant inhibitory activity on rhBChE (IC 50 , 15.44±0.91 μM). Furthermore, moderated DPPH⋅ scavenging, metal chelating activities, and low hemolysis evaluated in human erythrocytes were previously reported for this peptide [15] …”

Section: Resultssupporting

confidence: 56%

“…This inhibitory activity can be justified by the predicted interaction of W3 with key residues of the PAS as the Trp residue at its center [15] . Many reported anti‐aggregation compounds showed interactions with this residue [35–37] .…”

Section: Resultsmentioning

confidence: 95%

“…The design and synthesis of this peptide series were reported in a recent publication [15] . Concisely, 19‐mer peptide Hp‐1935 from B. pulchella was used as the base sequence.…”

Section: Resultsmentioning

confidence: 99%

“…Previous kinetics and computational studies had demonstrated that the inhibitory mechanism of the original peptide Hp‐1935 and its derivatives is of reversible non‐competitive type acting in the PAS. Herein, we studied the interactions of W3 on hAChE and W3W7 on hBChE at an atomistic level in silico [13,15] . We also performed kinetic measurements of the reaction of the best inhibitor to calculate its inhibitory constant (K i ).…”

Section: Resultsmentioning

confidence: 99%

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Inhibition of Human Cholinesterases and in vitro β‐Amyloid Aggregation by Rationally Designed Peptides

Sanchís

Spinelli

Dias³

et al. 2023

ChemMedChem

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The multifactorial nature of Alzheimer's disease (AD) is now widely recognized, which has increased the interest in compounds that can address more than one AD-associated targets. Herein, we report the inhibitory activity on the human cholinesterases (acetylcholinesterase, hAChE and butyrylcholinesterase, hBChE) and on the AChE-induced β-amyloid peptide (Aβ) aggregation by a series of peptide derivatives designed by mutating aliphatic residues for aromatic ones. We identified peptide W3 (LGWVSKGKLL-NH 2 ) as an interesting scaffold for the development of new anti-AD multitarget-directed drugs. It showed the lowest IC 50 value against hAChE reported for a peptide (0.99 � 0.02 μM) and inhibited 94.2 % � 1.2 of AChEinduced Aβ aggregation at 10 μM. Furthermore, it inhibited hBChE (IC 50 , 15.44 � 0.91 μM), showed no in vivo toxicity in brine shrimp and had shown moderated radical scavenging and Fe 2 + chelating capabilities in previous studies. The results are in line with multiple reports showing the utility of the indole moiety for the development of cholinesterase inhibitors.

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Section: Resultssupporting

confidence: 56%

Section: Resultsmentioning

confidence: 95%

“…The design and synthesis of this peptide series were reported in a recent publication [15] . Concisely, 19‐mer peptide Hp‐1935 from B. pulchella was used as the base sequence.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Inhibition of Human Cholinesterases and in vitro β‐Amyloid Aggregation by Rationally Designed Peptides

Sanchís

Spinelli

Dias³

et al. 2023

ChemMedChem

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“…The peptide BcI-1003 has been shown to have the ability to act on three key therapeutic targets of AD, inhibiting the activity of BChE and MAO-B enzymes, and showing a powerful and rapid antioxidant capability. Previous studies have shown that the modi cation of key residues to natural sequences managed to increase inhibitory activities of enzymes, as well as confer new activities(Sanchis et al 2020;Sanchis et al 2022). This kind of strategy could be a useful tool to improve the activity of the natural peptide BcI-1003 against BChE and MAO-B.…”

mentioning

confidence: 99%

Biological Characterization of Natural Peptide BcI-1003 from Boana cordobae (anura): Role in Alzheimer’s Disease and Microbial Infections

Spinelli

Humpola

Sanchís

et al. 2022

Int J Pept Res Ther

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Nature continues to be one of the most important sources of molecules for the development of novel therapeutic agents. The skin of anuran's (frogs and toads) is a rich source of peptides with a great importance in the search of bioactive agents applying to human health. Alzheimer's disease (AD) is a complex disease associated with numerous pathological pathways, making their simultaneous modulation necessary. On the other hand, the increasing bacterial resistance against conventional antibiotics has made it essential to search for new antimicrobial drugs with different modes of action. Here in we report the natural peptide BcI-1003, isolated from Boana cordobae amphibian skin, as an agent capable to act on three key therapeutic targets of AD, inhibiting the activity of BChE (IC 50 = 669 µM) and MAO-B (IC 50 = 570 µM) enzymes, and showing a powerful and rapid antioxidant activity (EC 50 = 7.24 µM). Besides, BcI-1003 showed antimicrobial activity against clinically drug-resistant gram-positive and gram-negative bacterial strains, with MIC values ranging from 8 to 127 µM against Staphylococcus aureus MR-1; S. aureus MR-2 and Escherichia coli MDR-1.

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Antioxidant peptides, the guardian of life from oxidative stress

Zhu,

Wang,

Jia

et al. 2023

Medicinal Research Reviews

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Reactive oxygen species (ROS) are produced during oxidative metabolism in aerobic organisms. Under normal conditions, ROS production and elimination are in a relatively balanced state. However, under internal or external environmental stress, such as high glucose levels or UV radiation, ROS production can increase significantly, leading to oxidative stress. Excess ROS production not only damages biomolecules but is also closely associated with the pathogenesis of many diseases, such as skin photoaging, diabetes, and cancer. Antioxidant peptides (AOPs) are naturally occurring or artificially designed peptides that can reduce the levels of ROS and other pro‐oxidants, thus showing great potential in the treatment of oxidative stress‐related diseases. In this review, we discussed ROS production and its role in inducing oxidative stress‐related diseases in humans. Additionally, we discussed the sources, mechanism of action, and evaluation methods of AOPs and provided directions for future studies on AOPs.

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Rational design and synthesis of modified natural peptides from Boana pulchella (anura) as acetylcholinesterase inhibitors and antioxidants

Cited by 6 publications

References 62 publications

Inhibition of Human Cholinesterases and in vitro β‐Amyloid Aggregation by Rationally Designed Peptides

Inhibition of Human Cholinesterases and in vitro β‐Amyloid Aggregation by Rationally Designed Peptides

Biological Characterization of Natural Peptide BcI-1003 from Boana cordobae (anura): Role in Alzheimer’s Disease and Microbial Infections

Antioxidant peptides, the guardian of life from oxidative stress

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