Human Il-2Rɑ Subunit Binding Modulation of Il-2 Through a Decline in Electrostatic Interactions: A Computational and Experimental Approach

Human Il-2Rɑ Subunit Binding Modulation of Il-2 Through a Decline in Electrostatic Interactions: A Computational and Experimental Approach Publisher Pubmed

Beig Parikhani A^{1, 2} ; Bagherzadeh K^{3, 4} ; Dehghan R^{1, 2} ; Biglari A⁵ ; Shokrgozar MA⁶ ; Riazi Rad F⁷ ; Zeinali S⁸ ; Talebkhan Y⁹ ; Ajdary S⁷ ; Ahangari Cohan R¹⁰ ; Behdani M¹

Show Affiliations

1. Venom and Biotherapeutics Molecules Laboratory, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
2. Student Research Committee, Pasteur Institute of Iran, Tehran, Iran
3. Stem Cell and Regenerative Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran
4. Eye Research Center, Five Senses Health Institute, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
5. School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
6. National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran
7. Department of Immunology, Pasteur Institute of Iran, Tehran, Iran
8. Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
9. Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
10. Department of Nanobiotechnology, New Technologies Research Group, Pasteur Institute of Iran, Tehran, Iran

Source: PloS one Published:2022

Abstract

Although high-dose IL-2 has clear antitumor effects, severe side effects like severe toxicity and activation of Tregs by binding of IL-2 to high-affinity IL-2R, hypotension, and vascular leak syndrome limit its applications as a therapeutic antitumor agent. Here in this study, a rational computational approach was employed to develop and design novel triple-mutant IL-2 variants with the aim of improving IL-2-based immunotherapy. The affinity of the mutants towards IL-2Rα was further computed with the aid of molecular dynamic simulations and umbrella sampling techniques and the obtained results were compared to those of wild-type IL-2. In vitro experiments by flow cytometry showed that the anti-CD25 mAb was able to bind to PBMC cells even after mutant 2 preincubation, however, the binding strength of the mutant to α-subunit was less than of wtIL-2. Additionally, reduction of IL-2Rα subunit affinity did not significantly disturb IL-2/IL2Rβγc subunits interactions.

Style	Citing Format
MLA	Beig Parikhani A, et al.. "Human Il-2Rɑ Subunit Binding Modulation of Il-2 Through a Decline in Electrostatic Interactions: A Computational and Experimental Approach." PloS one, vol. 17, no. 2, 2022, pp. e0264353-.
APA	Beig Parikhani A, Bagherzadeh K, Dehghan R, Biglari A, Shokrgozar MA, Riazi Rad F, Zeinali S, Talebkhan Y, Ajdary S, Ahangari Cohan R, Behdani M (2022). Human Il-2Rɑ Subunit Binding Modulation of Il-2 Through a Decline in Electrostatic Interactions: A Computational and Experimental Approach. PloS one, 17(2), e0264353-.
Chicago	Beig Parikhani A, Bagherzadeh K, Dehghan R, Biglari A, Shokrgozar MA, Riazi Rad F, Zeinali S, et al.. "Human Il-2Rɑ Subunit Binding Modulation of Il-2 Through a Decline in Electrostatic Interactions: A Computational and Experimental Approach." PloS one 17, no. 2 (2022): e0264353-.
Harvard	Beig Parikhani A et al. (2022) 'Human Il-2Rɑ Subunit Binding Modulation of Il-2 Through a Decline in Electrostatic Interactions: A Computational and Experimental Approach', PloS one, 17(2), pp. e0264353-.
Vancouver	Beig Parikhani A, Bagherzadeh K, Dehghan R, Biglari A, Shokrgozar MA, Riazi Rad F, et al.. Human Il-2Rɑ Subunit Binding Modulation of Il-2 Through a Decline in Electrostatic Interactions: A Computational and Experimental Approach. PloS one. 2022;17(2):e0264353-.
BibTex	@article{ author = {Beig Parikhani A and Bagherzadeh K and Dehghan R and Biglari A and Shokrgozar MA and Riazi Rad F and Zeinali S and Talebkhan Y and Ajdary S and Ahangari Cohan R and Behdani M}, title = {Human Il-2Rɑ Subunit Binding Modulation of Il-2 Through a Decline in Electrostatic Interactions: A Computational and Experimental Approach}, journal = {PloS one}, volume = {17}, number = {2}, pages = {e0264353-}, year = {2022} }
RIS	TY - JOUR AU - Beig Parikhani A AU - Bagherzadeh K AU - Dehghan R AU - Biglari A AU - Shokrgozar MA AU - Riazi Rad F AU - Zeinali S AU - Talebkhan Y AU - Ajdary S AU - Ahangari Cohan R AU - Behdani M TI - Human Il-2Rɑ Subunit Binding Modulation of Il-2 Through a Decline in Electrostatic Interactions: A Computational and Experimental Approach JO - PloS one VL - 17 IS - 2 SP - e0264353 EP - PY - 2022 ER -

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Abstract