Lysosome-targeting chimeras with different ratios and molecular weights, their preparation methods, and applications.

Abstract

This invention discloses lysosome-targeting chimeras based on different ratios and molecular weights, their preparation methods, and applications, belonging to the field of biomedical technology. Lysosome-targeting chimera (LYTAC) molecules contain target protein ligands, linkers, and lysosome-targeting receptor ligands. The core of this invention lies in systematically regulating the molecular weight ratio (range 1:1 to 1:10) between the target protein ligand and the lysosome-targeting receptor ligand, as well as the total molecular weight of LYTAC (range 1000 Da to 5000 Da), to obtain a series of LYTAC molecules with different properties. This invention provides a method for preparing the LYTAC molecules via chemical coupling. Experiments show that by optimizing the above parameters, the LYTAC molecules prepared by this invention can significantly improve the degradation efficiency and specificity of extracellular and membrane-associated target proteins (such as PD-L1, EGFR, etc.), while optimizing their pharmacokinetic properties, showing broad application prospects in the treatment of cancer, neurodegenerative diseases, and other fields.

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