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

Abstract

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

Keywords:

• SIKVAV
• integrin receptors
• α3β1 receptors
• α6β1 receptors
• cell proliferation
• tissue proliferation

Disclosure statement

The authors declare no conflict of interest in this work with any potentially affected party by the results of this study. The authors also declare no influence of any second party on designing of conducting the study.

Additional information

Funding

The authors would like to thank the financial support from the Federal University of Piauí, FAPEPI, CAPES, CNPq and FIOCRUZ.