Initial peptidomic profiling of Brazilian sea urchins: Arbacia lixula, Lytechinus variegatus and Echinometra lucunter

Sciani, Juliana Mozer; Emerenciano, Andrews Krupinski; Silva, José Roberto Machado Cunha da; Pimenta, Daniel C.

doi:10.1186/s40409-016-0071-x

Cited by 9 publications

(6 citation statements)

References 17 publications

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“…Peptides have been studied to inhibit BACE-1, and they are biomolecules that fill the gap between small molecules and protein drugs and share the advantages of both groups, namely, high stability and bioavailability (Bruno et al, 2013;Craik et al, 2013). Animal venoms and secretions (including marine ones) are rich in bioactive peptides, representing a successful group of molecules with high potency that are rarely studied and explored from a pharmacological aspect (Bhat et al, 2015;Sciani et al, 2016).…”

Section: Resultsmentioning

confidence: 99%

Design, in silico and pharmacological evaluation of a peptide inhibitor of BACE-1

Boldin,

Zychar,

Gonçalves

et al. 2023

Front. Pharmacol.

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Introduction: Alzheimer’s disease (AD) is the main type of dementia, caused by the accumulation of amyloid plaques, formed by amyloid peptides after being processed from amyloid precursor protein (APP) by γ- and ß-secretases (BACE-1). Although amyloid peptides have been well established for AD, they have been found in other neurodegenerative diseases, such as Parkinson’s disease, Lewy body dementia, and amyotrophic lateral sclerosis. Inhibitors of BACE-1 have been searched and developed, but clinical trials failed due to lack of efficacy or toxicity. Nevertheless, it is still considered a good therapeutic target, as it was proven to remove amyloid peptides and improve memory.Methods: In this work, we designed a peptide based on a sequence obtained from the marine fish Merluccius productus and evaluated it by molecular docking to verify its binding to BACE-1, which was tested experimentally by enzymatic kinetics and cell culture assays. The peptide was injected in healthy mice to study its pharmacokinetics and toxicity.Results: We could obtain a new sequence in which the first N-terminal amino acids and the last one bound to the catalytic site of BACE-1 and showed high stability and hydrophobicity. The synthetic peptide showed a competitive inhibition of BACE-1 and Ki = 94 nM, and when injected in differentiated neurons, it could reduce Aβ42o production. In plasma, its half-life is ∼1 h, clearance is 0.0015 μg/L/h, and Vss is 0.0015 μg/L/h. The peptide was found in the spleen and liver 30 min after injection and reduced its level after that, when it was quantified in the kidneys, indicating its fast distribution and urinary excretion. Interestingly, the peptide was found in the brain 2 h after its administration. Histological analysis showed no morphological alteration in any organ, as well as the absence of inflammatory cells, indicating a lack of toxicity.Discussion: We obtained a new BACE-1 inhibitor peptide with fast distribution to the tissues, without accumulation in any organ, but found in the brain, with the possibility to reach its molecular target, BACE-1, contributing to the reduction in the amyloid peptide, which causes amyloid-linked neurodegenerative diseases.

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Section: Resultsmentioning

confidence: 99%

Design, in silico and pharmacological evaluation of a peptide inhibitor of BACE-1

Boldin,

Zychar,

Gonçalves

et al. 2023

Front. Pharmacol.

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“…For the sea urchin L. variegatus , the coelomic fluid was obtained by inserting a needle into the peristomal cavity. The liquid was centrifuged at 3000 rpm and the supernatant stored at −20 °C [ 28 , 60 ].…”

Section: Methodsmentioning

confidence: 99%

Caspase-1 and Cathepsin B Inhibitors from Marine Invertebrates, Aiming at a Reduction in Neuroinflammation

et al. 2022

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Neuroinflammation is a condition associated with several types of dementia, such as Alzheimer’s disease (AD), mainly caused by an inflammatory response to amyloid peptides that induce microglial activation, with subsequent cytokine release. Neuronal caspase-1 from inflammasome and cathepsin B are key enzymes mediating neuroinflammation in AD, therefore, revealing new molecules to modulate these enzymes may be an interesting approach to treat neurodegenerative diseases. In this study, we searched for new caspase-1 and cathepsin B inhibitors from five species of Brazilian marine invertebrates (four cnidarians and one echinoderm). The results show that the extract of the box jellyfish Chiropsalmus quadrumanus inhibits caspase-1. This extract was fractionated, and the products monitored for their inhibitory activity, until the obtention of a pure molecule, which was identified as trigonelline by mass spectrometry. Moreover, four extracts inhibit cathepsin B, and Exaiptasia diaphana was selected for subsequent fractionation and characterization, resulting in the identification of betaine as being responsible for the inhibitory action. Both molecules are already found in marine organisms, however, this is the first study showing a potent inhibitory effect on caspase-1 and cathepsin B activities. Therefore, these new prototypes can be considered for the enzyme inhibition and subsequent control of the neuroinflammation.

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“…The peptides used in this study are based on Sciani et al (2016) research, namely peptides measuring 5-7 amino acids (Table 1). The 3D struc-ture of the peptides was modelled using the PEP-FOLD3 web server (https://bioserv.rpbs.univparis-diderot.fr/services/PEP-FOLD3/) with the de novo structure prediction method (Lamiable et al, 2016).…”

Section: Ligands Preparationmentioning

confidence: 99%

Molecular docking study of sea urchin (Arbacia lixula) peptides as multi-target inhibitor for non-small cell lung cancer (NSCLC) associated proteins

Widyananda¹,

Pratama²,

Samoedra³

et al. 2021

J Pharm Pharmacogn Res

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Context: Lung cancer is a type of cancer that causes the most deaths worldwide. The most common type of lung cancer is non-small cell lung cancer (NSCLC). Sea urchin (Arbacia lixula) has high potential as an anti-NSCLC agent. Aims: To analyze the anticancer activity of peptides from A. lixula coelomic fluid in inhibiting the activity of NSCLC-related proteins. Methods: Peptide modeling was performed using the PEP-FOLD3 web server. Proteins that have a crucial role in NSCLC progression were determined using KEGG pathway database. 3D protein structures such as EGFR, PI3K, BRAF V600E, and JAK3 were taken from the RCSB PDB database. Docking was performed using Autodock Vina software. Docking results analysis was carried out using Discovery Studio 2019 software. Results: Some peptides bind to the active sites with low binding affinity. Peptide 10 binds to the active site of the EGFR with a binding affinity of -9 kcal/mol. Peptide 5 binds to the active sites of PI3K and BRAF V600E with binding affinity of -8.2 and -8.1 kcal/mol, respectively. Peptide 11 binds to the active site of JAK3 with a binding affinity of -8.1 kcal/mol. All of these peptides have lower binding affinity than ATP as the native ligand. Besides, these peptides also produce more hydrogen bonds than ATP, so they are predicted to be more stable. Conclusions: Peptides 10, 5, and 11 have high potential as anti-NSCLC agents because they can inhibit the activity of proteins that play an essential role in the growth of NSCLC, namely EGFR, PI3K, BRAF V600E, and JAK3 through the competitive ATP inhibitor mechanism.

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Initial peptidomic profiling of Brazilian sea urchins: Arbacia lixula, Lytechinus variegatus and Echinometra lucunter

Cited by 9 publications

References 17 publications

Design, in silico and pharmacological evaluation of a peptide inhibitor of BACE-1

Design, in silico and pharmacological evaluation of a peptide inhibitor of BACE-1

Caspase-1 and Cathepsin B Inhibitors from Marine Invertebrates, Aiming at a Reduction in Neuroinflammation

Molecular docking study of sea urchin (Arbacia lixula) peptides as multi-target inhibitor for non-small cell lung cancer (NSCLC) associated proteins

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