GalNAc-L96 Intermediate (Triple-Target Head 2)

What is GalNAc-L96 Intermediate (Triple-Target Head 2)? GalNAc-L96 Intermediate (Triple-Target Head 2) is a high-purity, TFA-amine functionalized trivalent N-acetylgalactosamine cluster intermediate (CAS: 1159408-65-7). Specifically engineered as a key molecular building block for targeted nucleic acid delivery, it contains three per-acetylated GalNAc targeting units arranged around a central branching core, terminating in a reactive primary amine TFA salt ($\text{NH}_2 \cdot \text{TFA}$). This terminal amine serves as a direct anchor for functionalizing solid synthesis supports—such as co-polymer coated controlled pore glass (CPG)—or for solution-phase bioconjugation, providing medicinal chemists and process engineers with an efficient vehicle for liver-directed siRNA, antisense oligonucleotide (ASO), and microRNA delivery.

1. Product Description

GalNAc-L96 Intermediate (Triple-Target Head 2)

Product Overview

GalNAc-L96 Intermediate (Triple-Target Head 2) is a specialized structural intermediate synthesized to facilitate the automated preparation of liver-homing therapeutic oligonucleotides. The molecule displays three acetyl-protected GalNAc functional heads oriented in a defined spatial geometry that matches the subunit spacing of the hepatic asialoglycoprotein receptor (ASGPR).

Terminating in a single primary aliphatic amine salt ($\text{NH}_2 \cdot \text{TFA}$), this intermediate couples efficiently with carboxyl- or succinate-bearing matrices and synthetic linkers. This spatial clustering enables rapid, nanomolar-affinity binding to ASGPRs on hepatocytes, triggering efficient receptor-mediated endocytosis in vivo.

Key Technical Features

• Optimized Trivalent Cluster: Precisely spaced GalNAc arms deliver strong multivalent avidity toward hepatic ASGPR complexes, maximizing hepatocyte-specific cellular entry.

• Reactive TFA-Amine Handle ($\text{NH}_2 \cdot \text{TFA}$): Soluble, reactive primary amine salt enables high coupling yields when immobilizing onto succinylated solid supports or coupling to carboxylic acid-functionalized delivery vectors.

• Robust Hydroxyl Acetylation: Fully acetylated pyranose hydroxyl groups protect the saccharide units throughout downstream coupling chemistry and deprotect cleanly under standard basic cleavage conditions (e.g., aqueous ammonia or AMA).

• High Chemical Uniformity: Batch-controlled HPLC purity ensures minimal truncated or mono-/bis-branched side products during downstream solid support conjugation or solution bioconjugation.

Applications

• Custom CPG Solid Support Conjugation: Primary precursor for preparing pre-loaded 3′-GalNAc solid supports used in single-run automated synthesis of liver-targeting oligonucleotides.

• Targeted Bioconjugation: Direct covalent conjugation to activated oligonucleotides, lipid nanoparticles (LNPs), or peptides for hepatotropic drug delivery.

• ASGPR Receptor Kinetic Assays: Standard molecular ligand for in vitro binding assays and metabolic clearance profiling.

💡 Synthesis Optimization Note (Hyper-link CPG Pre-Loading Service)

While this product is supplied as a high-purity chemical intermediate corresponding directly to the structural formula, we also provide custom pre-loading onto our proprietary co-polymer coated CPG (Hyper-link CPG):

• 3× Higher Output & Lower COG: Hyper-link CPG delivers up to a 3× higher functional loading capacity than conventional un-coated glass supports, markedly reducing overall Cost of Goods (COG).

• ~30% Lower Purification Costs: Minimizes matrix leaching to deliver high Full-Length Product (FLP) purity directly from the column.

• Turnkey Convenience: Skip in-house loading, capping, and loading assay steps—receive synthesis-ready GalNAc-loaded bulk CPG powder or packed synthesis columns.