PD-L1 DNA aptamers isolated from agarose-bead SELEX.

Autor: Mohd Nazri MN; Institute for Research in Molecular Medicine (INFORMM), USM Health Campus, 16150 Kota Bharu, Kelantan, Malaysia. Electronic address: nnajmi@student.usm.my., Khairil Anwar NA; Institute for Research in Molecular Medicine (INFORMM), USM Health Campus, 16150 Kota Bharu, Kelantan, Malaysia. Electronic address: amira.anwar@student.usm.my., Mohd Zaidi NF; Institute for Research in Molecular Medicine (INFORMM), USM Health Campus, 16150 Kota Bharu, Kelantan, Malaysia. Electronic address: fatihah@usm.my., Fadzli Mustaffa KM; Institute for Research in Molecular Medicine (INFORMM), USM Health Campus, 16150 Kota Bharu, Kelantan, Malaysia. Electronic address: khairulmf@usm.my., Mokhtar NF; Institute for Research in Molecular Medicine (INFORMM), USM Health Campus, 16150 Kota Bharu, Kelantan, Malaysia. Electronic address: fatmawati@usm.my.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2024 Nov 01; Vol. 112, pp. 129943. Date of Electronic Publication: 2024 Aug 31.
DOI: 10.1016/j.bmcl.2024.129943
Abstrakt: Increased expression and activity of the PD-L1/PD-1 pathway suppresses the activation of cytotoxic T cells, which is vital in anti-tumour defence, allowing tumours to rise, expand and progress. Current strategies using antibodies to target PD-1/PD-L1 have been very effective in cancer therapeutics and companion diagnostics. Aptamers are a new class of molecules that offer an alternative to antibodies. Herein, the systematic evolution of ligands by exponential enrichment (SELEX) using agarose slurry beads was conducted to isolate DNA aptamers specific to recombinant human PD-L1 (rhPD-L1). Isolated aptamers were sequenced and analysed using MEGA X and structural features were examined using mFold. Three aptamer candidates (P33, P32, and P12) were selected for evaluation of binding affinity (dissociation constant, K d ) using ELONA and specificity and competitive inhibition assessment using the potentiostat-electrochemical method. Among those three, P32 displayed the highest specificity (8 nM) against PD-L1. However, P32 competes for the same binding site with the control antibody, 28-8. This study warrants further assessment of P32 aptamer as a potential, cost-effective alternative tool for targeting PD-L1.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier Ltd.)
Databáze: MEDLINE
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