GALA peptide improves the potency of nanobody-drug conjugates by lipid-induced helix formation

A novel nanobody-drug conjugate (NDC) was constructed by incorporating an amphipathic peptide, GALA, which improved the cytotoxicity by one to two orders of magnitude. Mechanistic studies demonstrate that tethering to lipids induces GALA to form a helix, which dramatically enhances endocytosis. Our...

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Bibliographic Details
Published inChemical communications (Cambridge, England) Vol. 57; no. 12; pp. 1434 - 1437
Main Authors Chen, Ya Jie, Deng, Qi Wen, Wang, Li, Guo, Xiao Chun, Yang, Jian Yuan, Li, Ting, Xu, Zhengshuang, Lee, Hon Cheung, Zhao, Yong Juan
Format Journal Article
LanguageEnglish
Published England Royal Society of Chemistry 15.02.2021
Subjects
Anticancer properties
Conjugates
Lipids
Peptides
Tethering
Toxicity
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Summary:A novel nanobody-drug conjugate (NDC) was constructed by incorporating an amphipathic peptide, GALA, which improved the cytotoxicity by one to two orders of magnitude. Mechanistic studies demonstrate that tethering to lipids induces GALA to form a helix, which dramatically enhances endocytosis. Our work provides a general strategy not only for improving the anti-cancer efficacy of protein-drug conjugates but also for increasing the efficiency of other types of endocytosis-dependent cell delivery. We generated a potent nanobody-drug conjugation by fusing GALA, which forms helix induced by lipids, enhances membrane binding, and consequently increase cytotoxicity. We provides new insights into the GALA peptide and might boost the field of NDCs.
Bibliography:10.1039/d0cc07706b
Electronic supplementary information (ESI) available. See DOI
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1359-7345
1364-548X
DOI:10.1039/d0cc07706b