دورية أكاديمية
A phage-displayed disulfide constrained peptide discovery platform yields novel human plasma protein binders.
| العنوان: | A phage-displayed disulfide constrained peptide discovery platform yields novel human plasma protein binders. |
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| المؤلفون: | Xinxin Gao, Harini Kaluarachchi, Yingnan Zhang, Sunhee Hwang, Rami N Hannoush |
| المصدر: | PLoS ONE, Vol 19, Iss 3, p e0299804 (2024) |
| بيانات النشر: | Public Library of Science (PLoS), 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | Disulfide constrained peptides (DCPs) show great potential as templates for drug discovery. They are characterized by conserved cysteine residues that form intramolecular disulfide bonds. Taking advantage of phage display technology, we designed and generated twenty-six DCP phage libraries with enriched molecular diversity to enable the discovery of ligands against disease-causing proteins of interest. The libraries were designed based on five DCP scaffolds, namely Momordica charantia 1 (Mch1), gurmarin, Asteropsin-A, antimicrobial peptide-1 (AMP-1), and potato carboxypeptidase inhibitor (CPI). We also report optimized workflows for screening and producing synthetic and recombinant DCPs. Examples of novel DCP binders identified against various protein targets are presented, including human IgG Fc, serum albumin, vascular endothelial growth factor-A (VEGF-A) and platelet-derived growth factor (PDGF). We identified DCPs against human IgG Fc and serum albumin with sub-micromolar affinity from primary panning campaigns, providing alternative tools for potential half-life extension of peptides and small protein therapeutics. Overall, the molecular diversity of the DCP scaffolds included in the designed libraries, coupled with their distinct biochemical and biophysical properties, enables efficient and robust identification of de novo binders to drug targets of therapeutic relevance. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1932-6203 |
| Relation: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0299804&type=printable; https://doaj.org/toc/1932-6203 |
| DOI: | 10.1371/journal.pone.0299804&type=printable |
| DOI: | 10.1371/journal.pone.0299804 |
| URL الوصول: | https://doaj.org/article/db99f590e84746bab2f519d2511bd2b0 |
| رقم الأكسشن: | edsdoj.b99f590e84746bab2f519d2511bd2b0 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0299804&type=printable |