Computational and experimental investigations of a novel aptamer targeting oxidized low-density lipoprotein.

Autor: Khongwichit S; Faculty of Medical Technology, Prince of Songkla University, Songkhla, 90110, Thailand; Division of Biological Science, Faculty of Science, Prince of Songkla University, Songkhla, 90110, Thailand., Nualla-Ong A; Division of Biological Science, Faculty of Science, Prince of Songkla University, Songkhla, 90110, Thailand; Center for Genomics and Bioinformatic Research, Faculty of Science, Prince of Songkla University, Songkhla, 90110, Thailand; Medical of Technology Service Center, Faculty of Medical Technology, Prince of Songkla University, Songkhla, 90110, Thailand., Prompat N; Faculty of Medical Technology, Prince of Songkla University, Songkhla, 90110, Thailand; Medical of Technology Service Center, Faculty of Medical Technology, Prince of Songkla University, Songkhla, 90110, Thailand., Amatatongchai M; Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ubon Ratchathani University, Ubon Ratchathani, 34190, Thailand., Lieberzeit PA; University of Vienna, Faculty for Chemistry, Department of Physical Chemistry, Vienna, 1090, Austria., Chunta S; Faculty of Medical Technology, Prince of Songkla University, Songkhla, 90110, Thailand. Electronic address: suticha.c@psu.ac.th.
Jazyk: angličtina
Zdroj: Computers in biology and medicine [Comput Biol Med] 2024 Sep; Vol. 180, pp. 108994. Date of Electronic Publication: 2024 Aug 08.
DOI: 10.1016/j.compbiomed.2024.108994
Abstrakt: Oxidized low-density lipoprotein (oxLDL) induces the formation of atherosclerotic plaques. Apolipoprotein B100 (apoB100) is a crucial protein component in low-density lipoprotein (LDL), which includes oxLDL. The oxidation of amino acids and subsequent alterations in their structure generate oxLDL, which is a significant biomarker for the initial phases of coronary artery disease. This study employed molecular docking and molecular dynamics utilizing the MM/GBSA method to identify aptamers with a strong affinity for oxidized apoB100. Molecular docking and molecular dynamics were performed on two sequences of the aptamer candidates (aptamer no.11 (AP11: 5'-CTTCGATGTAGTTTTTGTATGGGGTGCCCTGGTTCCTGCA-3') and aptamer no.26 (AP26: 5'-GCGAACTCGCGAATCCAGAACGGGCTCGGTCCCGGGTCGA-3')), yielding respective binding free energies of -149.08 kcal/mol and -139.86 kcal/mol. Interaction modeling of the simulation revealed a strong hydrogen bond between the AP11-oxidized apoB100 complexes. In an aptamer-based gold nanoparticle (AuNP) aggregation assay, AP11 exhibits a color shift from red to purple with the highest absorbance ratio, and shows strong binding affinity to oxLDL, correlating with the simulation model results. AP11 demonstrated the potential for application as a novel recognition element in diagnostic methodologies and may also contribute to future advancements in preventive therapies for coronary artery disease.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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