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Fluorescence Labeling of Anchor-Modified Mart-1 Peptide for Increasing Its Affinity for Hla-A*0201: Hit Two Targets With One Arrow Publisher Pubmed



Fattahi P1 ; Salehi N2 ; Azizi Z3 ; Mohammadi J4 ; Norouzy A5 ; Moazzeni SM1
Authors
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Authors Affiliations
  1. 1. Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  2. 2. Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran
  3. 3. Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Biomedical Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran
  5. 5. Bioprocess Engineering Department, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran

Source: Journal of Peptide Science Published:2023


Abstract

One of the most successful strategies in designing peptide-based cancer vaccines is modifying natural epitope peptides to increase their binding strength to human leukocyte antigens (HLAs). Anchor-modified Mart-1 peptide (ELAGIGILTV) is among the artificial epitope peptides with the highest binding affinity for HLA-A*0201. In this study, by fluorescence labeling of its either C- or N-terminus with Nε-(5-carboxyfluorescein)-l-lysine, we not only made it traceable but also drastically increased its binding strength to HLA-A*0201. HLA streptamer, for the first time, is introduced for measuring the binding constants (Ka) of the labeled peptides. The affinity of the labeled peptides for the HLA-A*201 of the MCF-7 cells was extraordinarily high and co-incubating them with the highest possible amount of the unlabeled peptide, as a competitor, did not significantly prohibit them from binding to the HLA. The reproducibility of the obtained results was confirmed by using the T2 cell line. The HLA-deficient K562 cell line was used as the negative control. With in silico simulations, we found two hydrophobic pockets on both sides of HLA-A*0201 for anchoring the C- or N-terminal 5-carboxyfluorescein probe, which can explain the extraordinary affinity of the labeled peptides for the HLA-A*0201. © 2023 European Peptide Society and John Wiley & Sons, Ltd.
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