mPEG2-SH, namely Methyl Diethylene Glycol Thiol (2-(2-methoxyethoxy)ethane-1-thiol), is a monodisperse, short-chain polyethylene glycol (PEG) derivative. It features a well-defined molecular structure and a single molecular weight, consisting of a methoxy cap, two ethylene glycol units, and a terminal thiol (-SH) group. Compared to polydisperse PEG, monodisperse PEG offers advantages such as uniform molecular weight, high batch-to-batch reproducibility, and ease of purification and characterization, making it valuable for applications including gold nanoparticle modification, bioconjugation, and molecular linker design.

I. Basic Information

II. Structural Characteristics and Mechanism of Action

mPEG2-SH consists of precisely two ethylene glycol units with a single molecular weight, minimizing the impact of PEG molecular weight distribution variability on experimental result analysis. The terminal thiol (-SH) group serves as the core functional site with dual conjugation capabilities:

• Gold–Sulfur (Au–S) Bonding:Exhibits high affinity for noble metal surfaces such as gold and silver, forming stable surface modification layers suitable for gold nanoparticle modification and biosensor construction.

• Thioether Bond Formation:Undergoes thiol–maleimide coupling reactions (typically at pH 6.5–7.5) with maleimide groups, enabling site-specific PEGylation of biomacromolecules such as proteins and antibodies.

The PEG segment imparts good water solubility and biocompatibility to the molecule. The short-chain PEG structure helps reduce steric hindrance and is suitable for applications requiring precise control over modification layer thickness.

III. Main Applications

• Gold Nanoparticle Modification:Forms stable covalent conjugation through Au–S bonds, improving nanoparticle dispersion stability, biocompatibility, and reducing particle aggregation.

• Site-Specific Protein PEGylation:The thiol group undergoes specific coupling with maleimide, enabling site-directed modification of proteins, antibodies, and other biomacromolecules.

• Bioconjugation and Molecular Linkers:Serves as a short PEG connecting unit for modulating spatial distance and flexibility between biomolecules and functional small molecules, with potential applications in ADC, PROTAC, and chemical biology molecular design.

• Self-Assembled Monolayers and Biosensors:Utilizes the binding capability of thiol groups to metal surfaces to construct functionalized surfaces, reducing non-specific adsorption and enhancing detection signal stability.

IV. Related PEG Derivatives