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Affinity‐Directed Site‐Specific Protein Labeling and Its Application to Antibody‐Drug Conjugates

Authors
 Sooin Kim  ;  Sanggil Kim  ;  Sangji Kim  ;  Namkyoung Kim  ;  Sang Won Lee  ;  Hanbin Yi  ;  Seungeun Lee  ;  Taebo Sim  ;  Yongseok Kwon  ;  Hyun Soo Lee 
Citation
 ADVANCED SCIENCE, Vol.11(4) : e2306401, 2024-01 
Journal Title
ADVANCED SCIENCE
ISSN
 * 
Issue Date
2024-01
MeSH
Antibodies ; Immunoconjugates* ; Proteins / metabolism
Keywords
antibody-drug conjugates ; bioorthogonal chemistry ; genetic code expansion ; native protein labeling ; small helical binding protein
Abstract
Chemically modified proteins have diverse applications; however, conventional chemo-selective methods often yield heterogeneously labeled products. To address this limitation, site-specific protein labeling holds significant potential, driving extensive research in this area. Nevertheless, site-specific modification of native proteins remains challenging owing to the complexity of their functional groups. Therefore, a method for site-selective labeling of intact proteins is aimed to design. In this study, a novel approach to traceless affinity-directed intact protein labeling is established, which leverages small binding proteins and genetic code expansion technology. By applying this method, a site-specific antibody labeling with a drug, which leads to the production of highly effective antibody-drug conjugates specifically targeting breast cancer cell lines is achieved. This approach enables traceless conjugation of intact target proteins, which is a critical advantage in pharmaceutical applications. Furthermore, small helical binding proteins can be easily engineered for various target proteins, thereby expanding their potential applications in diverse fields. This innovative approach represents a significant advancement in site-specific modification of native proteins, including antibodies. It also bears immense potential for facilitating the development of therapeutic agents for various diseases.
Files in This Item:
T202401520.pdf Download
DOI
10.1002/advs.202306401
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Sim, Taebo(심태보)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/198703
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