Analysis of SIKVAV's receptor affinity, pharmacokinetics, and pharmacological characteristics: a matrikine with potent biological function.

Autor: Filgueiras LA; Laboratory of Innovation in Science and Technology - LACITEC, Department of Biophysics and Physiology, Federal University of Piauí, Teresina, Brazil., de Andrade FDCP; Laboratory of Innovation in Science and Technology - LACITEC, Department of Biophysics and Physiology, Federal University of Piauí, Teresina, Brazil., Iwao Horita S; Laboratory of Innovation in Therapies, Education, and Bioproducts - LITEB, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Shirsat SD; Laboratory of Innovation in Therapies, Education, and Bioproducts - LITEB, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Achal V; Environmental Engineering Program, Guangdong Technion - Israel Institute of Technology, Shantou, China.; Technion - Israel Institute of Technology, Haifa, Israel., Rai M; Department of Biotechnology, SGB Amravati University, Amravati, India., Henriques-Pons A; Laboratory of Innovation in Therapies, Education, and Bioproducts - LITEB, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Mendes AN; Laboratory of Innovation in Science and Technology - LACITEC, Department of Biophysics and Physiology, Federal University of Piauí, Teresina, Brazil.
Jazyk: angličtina
Zdroj: Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2024 Feb 12, pp. 1-23. Date of Electronic Publication: 2024 Feb 12.
DOI: 10.1080/07391102.2024.2313709
Abstrakt: Matrikines are biologically active peptides generated from fragments fragmentation of extracellular matrix components (ECM) that are functionally distinct from the original full-length molecule. The active matricryptic sites can be unmasked by ECM components enzymatic degradation or multimerization, heterotypic binding, adsorption to other molecules, cell-mediated mechanical forces, exposure to reactive oxygen species, ECM denaturation, and others. Laminin α1-derived peptide (SIKVAV) is a bioactive peptide derived from laminin-111 that participates in tumor development, cell proliferation, angiogenesis in various cell types. SIKVAV has also a potential pharmaceutical activity that may be used for tissue regeneration and bioengineering in Alzheimer's disease and muscular dystrophies. In this work, we made computational analyzes of SIKVAV regarding the ADMET panel, that stands for Administration, Distribution, Metabolism, Excretion, and Toxicity. Docking analyzes using the α3β1 and α6β1 integrin receptors were performed to fill in the gaps in the SIKVAV's signaling pathway and coupling tests showed that SIKVAV can interact with both receptors. Moreover, there is no indication of cytotoxicity, mutagenic or carcinogenic activity, skin or oral sensitivity. Our analysis suggests that SIKVAV has a high probability of interacting with peroxisome proliferator-activated receptor-gamma (NR-PPAR-γ), which has anti-inflammatory activity. The results of bioinformatics can help understand the participation of SIKVAV in homeostasis and influence the understanding of how this peptide can act as a biological asset in the control of dystrophies, neurodegenerative diseases, and tissue engineering.Communicated by Ramaswamy H. Sarma.
Databáze: MEDLINE