Reference - Detail
| RRC ID | 63304 |
|---|---|
| Author | Mihara E, Watanabe S, Bashiruddin NK, Nakamura N, Matoba K, Sano Y, Maini R, Yin Y, Sakai K, Arimori T, Matsumoto K, Suga H, Takagi J. |
| Title | Lasso-grafting of macrocyclic peptide pharmacophores yields multi-functional proteins. |
| Journal | Nat Commun |
| Abstract |
Protein engineering has great potential for devising multifunctional recombinant proteins to serve as next-generation protein therapeutics, but it often requires drastic modifications of the parental protein scaffolds e.g., additional domains at the N/C-terminus or replacement of a domain by another. A discovery platform system, called RaPID (Random non-standard Peptides Integrated Discovery) system, has enabled rapid discovery of small de novo macrocyclic peptides that bind a target protein with high binding specificity and affinity. Capitalizing on the optimized binding properties of the RaPID-derived peptides, here we show that RaPID-derived pharmacophore sequences can be readily implanted into surface-exposed loops on recombinant proteins and maintain both the parental peptide binding function(s) and the host protein function. We refer to this protein engineering method as lasso-grafting and demonstrate that it can endow specific binding capacity toward various receptors into a diverse set of scaffolds that includes IgG, serum albumin, and even capsid proteins of adeno-associated virus, enabling us to rapidly formulate and produce bi-, tri-, and even tetra-specific binder molecules. |
| Volume | 12(1) |
| Pages | 1543 |
| Published | 2021-3-9 |
| DOI | 10.1038/s41467-021-21875-0 |
| PII | 10.1038/s41467-021-21875-0 |
| PMID | 33750839 |
| PMC | PMC7943567 |
| MeSH | Capsid Proteins / chemistry Carrier Proteins / chemistry Cell Line Dependovirus Humans Immunoglobulin G / chemistry Models, Molecular Peptides / chemistry* Peptides / pharmacology* Protein Engineering / methods* Serum Albumin / chemistry Small Molecule Libraries |
| IF | 12.121 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 17 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | Jurkat |