| 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
|
| Resource |
| Human and Animal Cells |
Jurkat |
