Tri-GalNAc-PEG4-Azide is a N-acetylgalactosamine molecule which leverages three terminal beta-GalNAc (N-acetylgalactosamine) sugars for efficient binding to asialoglycoprotein receptors (ASGPR) expressed on liver cells (hepatocytes). The presence of the linker (beta-alanine) and the spacer (PEG4) influences the pharmacokinetics of the conjugate. The key functional group is the terminal azido allows for conjugation to various payloads containing alkyne groups through copper-catalyzed Azido-Alkyne Chemistry (CuAAC) or copper-free Azido-DBCO click reaction. The azido functional group facilitates the development of targeted conjugates for hepatocyte delivery. Upon binding to ASGPR, tri-b-GalNAc-b-alanine-PEG3-azide conjugates are rapidly taken up by hepatocytes via endocytosis, enabling researchers to deliver therapeutic cargo (drugs, siRNA) specifically to the liver. It can also be used to generate LYTACs, or labeled with dye for tissue imaging.
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