Mal-amido-PEG8-TFP ester
[CAS# 1924596-31-5]

Identification

• Classification: Chemical reagent >> Organic reagent >> Amide
• Name: Mal-amido-PEG8-TFP ester
• Synonyms: (2,3,5,6-tetrafluorophenyl) 3-[2-[2-[2-[2-[2-[2-[2-[2-[3-(2,5-dioxopyrrol-1-yl)propanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoate
• Molecular Formula: C₃₂H₄₄F₄N₂O₁₃
• Molecular Weight: 740.69
• CAS Registry Number: 1924596-31-5
• SMILES: C1=CC(=O)N(C1=O)CCC(=O)NCCOCCOCCOCCOCCOCCOCCOCCOCCC(=O)OC2=C(C(=CC(=C2F)F)F)F

Properties

• Density: 1.3±0.1 g/cm³ Calc.^*
• Boiling point: 780.6±60.0 ºC 760 mmHg (Calc.)^*
• Flash point: 425.9±32.9 ºC (Calc.)^*
• Index of refraction: 1.497 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319
• Precautionary Statements: P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330

Discovory and Applicatios

The chemical substance Mal-amido-PEG8-TFP ester, a polyethylene glycol (PEG)-based linker with maleimide and tetrafluorophenyl (TFP) ester functional groups, is widely used in bioconjugation and pharmaceutical chemistry. Its discovery and applications are well-documented in the literature, rooted in the development of PEGylation and heterobifunctional linker technologies.

The origins of Mal-amido-PEG8-TFP ester are tied to the evolution of PEG linkers, which gained prominence in the 1970s for their ability to improve the solubility, stability, and pharmacokinetics of biomolecules. The maleimide group, known since the mid-20th century for its selective reactivity with thiols, and the TFP ester, developed in the 1990s as a more hydrolytically stable alternative to N-hydroxysuccinimide (NHS) esters, were combined with PEG chains to create versatile bioconjugation reagents. The specific Mal-amido-PEG8-TFP ester, with an eight-unit PEG spacer, emerged in the late 20th and early 21st centuries to meet the pharmaceutical industry’s need for water-soluble, heterobifunctional linkers for applications like antibody-drug conjugates (ADCs) and protein PEGylation. Advances in PEG synthesis and functionalization enabled the precise construction of such compounds.

Synthetically, Mal-amido-PEG8-TFP ester (CAS: 1924596-31-5, molecular formula: C32H44F4N2O13) is prepared by functionalizing a PEG8 chain with a maleimide group at one end and a TFP ester at the other, linked through an amide bond. The process typically starts with a PEG8-diamine or PEG8-carboxylic acid, where the maleimide is introduced via reaction with maleic anhydride followed by cyclization, and the TFP ester is formed by coupling 2,3,5,6-tetrafluorophenol with a carboxylic acid group using a coupling agent like dicyclohexylcarbodiimide. These steps rely on well-established PEG chemistry protocols, ensuring high purity (≥95%) and functionality.
The primary application of Mal-amido-PEG8-TFP ester is as a bioconjugation linker in pharmaceutical research. The maleimide group reacts selectively with thiol groups (e.g., cysteine residues in proteins) between pH 6.5 and 7.5, forming a stable thioether bond, while the TFP ester reacts with primary amines (e.g., lysine residues) to form amide bonds, offering greater hydrolytic stability than NHS esters. The hydrophilic PEG8 spacer enhances water solubility and reduces aggregation of conjugated molecules, improving their pharmacokinetic properties. This linker is widely used in the synthesis of ADCs, protein-drug conjugates, and PROTACs (proteolysis-targeting chimeras), where it facilitates site-specific conjugation to improve drug delivery and efficacy. It is also employed in biomaterials and hydrogel synthesis, creating biocompatible networks for tissue engineering.In academic research, the compound is used to study bioconjugation mechanisms, PEGylation effects on protein stability, and the reactivity of maleimide and TFP ester groups. Its synthesis has contributed to the development of advanced PEG linkers with tailored chain lengths and functionalities. The compound is available commercially from suppliers like AxisPharm and BroadPharm, typically as a reagent-grade product for research purposes.The significance of Mal-amido-PEG8-TFP ester lies in its role as a heterobifunctional linker that combines the selective reactivity of maleimide and TFP ester with the solubility-enhancing properties of PEG. Its development reflects progress in bioconjugation chemistry and PEGylation techniques. By enabling precise, stable conjugation of biomolecules, it has become a critical tool in advancing pharmaceutical, biomaterial, and chemical research.