A Novel Type of PD-L1 Inhibitor rU1 snRNPA From Human-Derived Protein Scaffolds Library

Three marketed anti-PD-L1 antibodies almost have severe immune-mediated side effects. The therapeutic effects of anti-PD-L1 chemical inhibitors are not satisfied in the clinical trials. Here we constructed human-derived protein scaffolds library and screened scaffolds with a shape complementary to t...

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Autores principales:	Chuang Ma, Sennan Qiao, Zhiyi Liu, Liang Shan, Chongyang Liang, Meiling Fan, Fei Sun
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	PD-L1 inhibitor human-derived scaffold melanoma breast cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/09525b623e454bf2bbae4966a3b7676f
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spelling	oai:doaj.org-article:09525b623e454bf2bbae4966a3b7676f2021-12-01T12:36:11ZA Novel Type of PD-L1 Inhibitor rU1 snRNPA From Human-Derived Protein Scaffolds Library2234-943X10.3389/fonc.2021.781046https://doaj.org/article/09525b623e454bf2bbae4966a3b7676f2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.781046/fullhttps://doaj.org/toc/2234-943XThree marketed anti-PD-L1 antibodies almost have severe immune-mediated side effects. The therapeutic effects of anti-PD-L1 chemical inhibitors are not satisfied in the clinical trials. Here we constructed human-derived protein scaffolds library and screened scaffolds with a shape complementary to the PD-1 binding domain of PD-L1. The RNA binding domain of U1 snRNPA was selected as one of potential binders because it had the most favorable binding energies with PD-L1 and conformed to pre-established biological criteria for the screening of candidates. The recombinant U1 snRNPA (rU1 snRNPA) in Escherichia coli exhibits anti-cancer activity in melanoma and breast cancer by reactivating tumor-suppressed T cells in vitro and anti-melanoma activity in vivo. Considering hydrophobic and electrostatic interactions, three residues were mutated on the interface of U1 snRNPA and PD-L1 complex, and the ranked variants by PatchDock and A32D showed an increased active phenotype. The screening of human-derived protein scaffolds may become the potential development of therapeutic agents.Chuang MaSennan QiaoZhiyi LiuLiang ShanChongyang LiangMeiling FanFei SunFrontiers Media S.A.articlePD-L1inhibitorhuman-derivedscaffoldmelanomabreast cancerNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	PD-L1 inhibitor human-derived scaffold melanoma breast cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	PD-L1 inhibitor human-derived scaffold melanoma breast cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Chuang Ma Sennan Qiao Zhiyi Liu Liang Shan Chongyang Liang Meiling Fan Fei Sun A Novel Type of PD-L1 Inhibitor rU1 snRNPA From Human-Derived Protein Scaffolds Library
description	Three marketed anti-PD-L1 antibodies almost have severe immune-mediated side effects. The therapeutic effects of anti-PD-L1 chemical inhibitors are not satisfied in the clinical trials. Here we constructed human-derived protein scaffolds library and screened scaffolds with a shape complementary to the PD-1 binding domain of PD-L1. The RNA binding domain of U1 snRNPA was selected as one of potential binders because it had the most favorable binding energies with PD-L1 and conformed to pre-established biological criteria for the screening of candidates. The recombinant U1 snRNPA (rU1 snRNPA) in Escherichia coli exhibits anti-cancer activity in melanoma and breast cancer by reactivating tumor-suppressed T cells in vitro and anti-melanoma activity in vivo. Considering hydrophobic and electrostatic interactions, three residues were mutated on the interface of U1 snRNPA and PD-L1 complex, and the ranked variants by PatchDock and A32D showed an increased active phenotype. The screening of human-derived protein scaffolds may become the potential development of therapeutic agents.
format	article
author	Chuang Ma Sennan Qiao Zhiyi Liu Liang Shan Chongyang Liang Meiling Fan Fei Sun
author_facet	Chuang Ma Sennan Qiao Zhiyi Liu Liang Shan Chongyang Liang Meiling Fan Fei Sun
author_sort	Chuang Ma
title	A Novel Type of PD-L1 Inhibitor rU1 snRNPA From Human-Derived Protein Scaffolds Library
title_short	A Novel Type of PD-L1 Inhibitor rU1 snRNPA From Human-Derived Protein Scaffolds Library
title_full	A Novel Type of PD-L1 Inhibitor rU1 snRNPA From Human-Derived Protein Scaffolds Library
title_fullStr	A Novel Type of PD-L1 Inhibitor rU1 snRNPA From Human-Derived Protein Scaffolds Library
title_full_unstemmed	A Novel Type of PD-L1 Inhibitor rU1 snRNPA From Human-Derived Protein Scaffolds Library
title_sort	novel type of pd-l1 inhibitor ru1 snrnpa from human-derived protein scaffolds library
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/09525b623e454bf2bbae4966a3b7676f
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A Novel Type of PD-L1 Inhibitor rU1 snRNPA From Human-Derived Protein Scaffolds Library

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