Design of protein-binding peptides with controlled binding affinity: the case of SARS-CoV-2 receptor binding domain and angiotensin-converting enzyme 2 derived peptides
Rattachement africain : it. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
The development of methods able to modulate the binding affinity between proteins and peptides is of paramount biotechnological interest in view of a vast range of applications that imply designed polypeptides capable to impair or favour Protein-Protein Interactions. Here, we applied a peptide design algorithm based on shape complementarity optimization and electrostatic compatibility and provided the first experimental in vitro proof of the efficacy of the design algorithm. Focusing on the interaction between the SARS-CoV-2 Spike Receptor-Binding Domain (RBD) and the human angiotensin-converting enzyme 2 (ACE2) receptor, we extracted a 23-residues long peptide that structurally mimics the major interacting portion of the ACE2 receptor and designed in silico five mutants of such a peptide with a modulated affinity. Remarkably, experimental KD measurements, conducted using biolayer interferometry, matched the in silico predictions. Moreover, we investigated the molecular determinants that govern the variation in binding affinity through molecular dynamics simulation, by identifying the mechanisms driving the different values of binding affinity at a single residue level. Finally, the peptide sequence with the highest affinity, in comparison with the wild type peptide, was expressed as a fusion protein with human H ferritin (HFt) 24-mer. Solution measurements performed on the latter constructs confirmed that peptides still exhibited the expected trend, thereby enhancing their efficacy in RBD binding. Altogether, these results indicate the high potentiality of this general method in developing potent high-affinity vectors for hindering/enhancing protein-protein associations.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Design of protein-binding peptides with controlled binding affinity: the case of SARS-CoV-2 receptor binding domain and angiotensin-converting enzyme 2 derived peptides
- Date Crossref
- 05/01/2024
- Éditeur
- Frontiers Media SA
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Sapienza University of Rome pays non établi dans la noticeUniversité ou école supérieure
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Italian Institute of Technology pays non établi dans la noticeStructure de recherche
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Department of Basic and Applied Sciences for Engineering (SBAI) pays non établi dans la noticeInstitution
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Department of Biochemical Sciences "Alessandro Rossi Fanelli" pays non établi dans la noticeInstitution
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Centre for Human Technologies (CHT) pays non établi dans la noticeInstitution
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Department of Biology and Biotechnologies "Charles Darwin" pays non établi dans la noticeInstitution
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Center for Life Nano and Neuro Science pays non établi dans la noticeInstitution
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Department of Physics pays non établi dans la noticeInstitution
Sapienza University of Rome, Italian Institute of Technology et Department of Basic and Applied Sciences for Engineering (SBAI), avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.