Selection and evolution of disulfide-rich peptides via cellular protein quality control.

Selection and evolution of disulfide-rich peptides via cellular protein quality control.
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DOI:
10.1039/d2sc05343h
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发表时间:
2023-03-29
期刊:
影响因子:
8.4
通讯作者:
--
中科院分区:
化学1区
文献类型:
--
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Disulfide-rich peptides (DRPs) are an interesting and promising molecular format for drug discovery and development. However, the engineering and application of DRPs rely on the foldability of the peptides into specific structures with correct disulfide pairing, which strongly hinders the development of designed DRPs with randomly encoded sequences. Design or discovery of new DRPs with robust foldability would provide valuable scaffolds for developing peptide-based probes or therapeutics. Herein we report a cell-based selection system leveraging cellular protein quality control (termed PQC-select) to select DRPs with robust foldability from random sequences. By correlating the foldability of DRPs with their expression levels on the cell surface, thousands of sequences that can fold properly have been successfully identified. We anticipated that PQC-select will be applicable to many other designed DRP scaffolds in which the disulfide frameworks and/or the disulfide-directing motifs can be varied, enabling the generation of a variety of foldable DRPs with new structures and superior potential for further developments. A selection system leveraging cellular protein quality control (termed PQC-select) has been designed to select DRPs with robust foldability from random sequences, providing valuable scaffolds for developing peptide-based probes or therapeutics.
DOI: 10.1126/science.aaw2493
发表时间: 2019-03-22
期刊: SCIENCE
影响因子: 56.9
作者:
Shen, Huaizong;Liu, Dongliang;Yan, Nieng
通讯作者: Yan, Nieng
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Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
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发表时间: 2017-10-05
期刊: Nature
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Chevalier A;Silva DA;Rocklin GJ;Hicks DR;Vergara R;Murapa P;Bernard SM;Zhang L;Lam KH;Yao G;Bahl CD;Miyashita SI;Goreshnik I;Fuller JT;Koday MT;Jenkins CM;Colvin T;Carter L;Bohn A;Bryan CM;Fernández-Velasco DA;Stewart L;Dong M;Huang X;Jin R;Wilson IA;Fuller DH;Baker D
通讯作者: Baker D
DOI: 10.1038/nature19791
发表时间: 2016-10-20
期刊: NATURE
影响因子: 64.8
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Bhardwaj, Gaurav;Mulligan, Vikram Khipple;Bahl, Christopher D.;Gilmore, Jason M.;Harvey, Peta J.;Cheneval, Olivier;Buchko, Garry W.;Pulavarti, Surya V. S. R. K.;Kaas, Quentin;Eletsky, Alexander;Huang, Po-Ssu;Johnsen, William A.;Greisen, Per Jr;Rocklin, Gabriel J.;Song, Yifan;Linsky, Thomas W.;Watkins, Andrew;Rettie, Stephen A.;Xu, Xianzhong;Carter, Lauren P.;Bonneau, Richard;Olson, James M.;Coutsias, Evangelos;Correnti, Colin E.;Szyperski, Thomas;Craik, David J.;Baker, David
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DOI: 10.1089/ars.2008.2295
发表时间: 2009-05-01
影响因子: 6.6
作者:
Gunasekera, Sunithi;Daly, Norelle L.;Craik, David J.
通讯作者: Craik, David J.