GALA peptide improves the potency of nanobody–drug conjugates by lipid-induced helix formation
Ya Jie Chen, Qi Deng, Li Wang, Xiao Chun Guo, Jian Yuan Yang, Ting Li, Zhengshuang Xu, Hon Cheung Lee, Yong Zhao
Abstract
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.
Topics & Concepts
ConjugateChemistryPeptideCytotoxicityHelix (gastropod)DrugPotencyBiochemistryCombinatorial chemistryStereochemistryPharmacologyBiophysicsIn vitroBiologyMathematical analysisMathematicsSnailEcologyGlycosylation and Glycoproteins ResearchMonoclonal and Polyclonal Antibodies ResearchBiochemical and Structural Characterization