Methyl-PEG4-acyl chloride

 CAS No.: 62124-69-0  Cat No.: BP-501578 4.5  

Methyl-PEG4-acyl chloride is an acyl chloride–functionalized polyethylene glycol (PEG) linker designed for PROTAC synthesis and other bioconjugation workflows. Structurally, it comprises a methyl-terminated PEG chain of four ethylene glycol units bearing a reactive acyl chloride at one end, enabling efficient formation of amide bonds with amine-containing ligands under standard acylation conditions. In PROTAC architectures, such PEG-based linkers are widely used to tune the effective distance, conformational flexibility, and solvation of the conjugate, which can improve productive ternary complex formation between a target-binding moiety and an E3 ligase ligand. The acyl chloride handle provides a straightforward route to install the linker onto carboxylate or amine-bearing components, facilitating modular assembly of degraders. Its PEG character can also enhance aqueous compatibility and reduce nonspecific hydrophobic interactions, supporting more reproducible linker-mediated coupling during targeted protein degradation research.

Methyl-PEG4-acyl chloride

Structure of 62124-69-0

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PROTAC Linker
Molecular Formula
C₁₀H₁₉ClO₆
Molecular Weight
270.71

* For research and manufacturing use only. Not for human or clinical use.

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IUPACName
2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethyl carbonochloridate
InChI Key
HLNFSOCHAKDRBH-UHFFFAOYSA-N
InChI
InChI=1S/C10H19ClO6/c1-13-2-3-14-4-5-15-6-7-16-8-9-17-10(11)12/h2-9H2,1H3
SMILES
COCCOCCOCCOCCOC(=O)Cl
1. Chloride toxicity in critically ill patients: What's the evidence?
Sabri Soussi, Axelle Ferry, Maité Chaussard, Matthieu Legrand Anaesth Crit Care Pain Med. 2017 Apr;36(2):125-130.doi: 10.1016/j.accpm.2016.03.008.Epub 2016 Jul 28.
Crystalloids have become the fluid of choice in critically ill patients and in the operating room both for fluid resuscitation and fluid maintenance. Among crystalloids, NaCl 0.9% has been the most widely used fluid. However, emerging evidence suggests that administration of 0.9% saline could be harmful mainly through high chloride content and that the use of fluid with low chloride content may be preferable in major surgery and intensive care patients. Administration of NaCl 0.9% is the leading cause of metabolic hyperchloraemic acidosis in critically ill patients and side effects might target coagulation, renal function, and ultimately increase mortality. More balanced solutions therefore may be used especially when large amount of fluids are administered in high-risk patients. In this review, we discuss physiological background favouring the use of balanced solutions as well as the most recent clinical data regarding the use of crystalloid solutions in critically ill patients and patients undergoing major surgery.
2. Development and biological applications of chloride-sensitive fluorescent indicators
A S Verkman Am J Physiol. 1990 Sep;259(3 Pt 1):C375-88.doi: 10.1152/ajpcell.1990.259.3.C375.
Chloride movement across cell plasma and internal membranes, is of central importance for regulation of cell volume and pH, vectorial salt movement in epithelia, and, probably, intracellular traffic. Quinolinium-based chloride-sensitive fluorescent indicators provide a new approach to study chloride transport mechanisms and regulation that is complementary to 36Cl tracer methods, intracellular microelectrodes, and patch clamp. Indicator fluorescence is quenched by chloride by a collisional mechanism with Stern-Volmer constants of up to 220 M-1. Fluorescence is quenched selectively by chloride in physiological systems and responds to changes in chloride concentration in under 1 ms. The indicators are nontoxic and can be loaded into living cells for continuous measurement of intracellular chloride concentration by single-cell fluorescence microscopy. In this review, the structure-activity relationships for chloride-sensitive fluorescent indicators are described. Methodology for measurement of chloride transport in isolated vesicle and liposome systems and in intact cells is evaluated critically by use of examples from epithelial cell physiology. Future directions for synthesis of tailored chloride-sensitive indicators and new applications of indicators for studies of transport regulation and intracellular ion gradients are proposed.
3. A Quick Reference on Chloride
Andrea A Bohn, Helio Autran de Morais Vet Clin North Am Small Anim Pract. 2017 Mar;47(2):219-222.doi: 10.1016/j.cvsm.2016.10.008.Epub 2016 Dec 20.
Chloride is an essential element, playing important roles in digestion, muscular activity, regulation of body fluids, and acid-base balance. As the most abundant anion in extracellular fluid, chloride plays a major role in maintaining electroneutrality. Chloride is intrinsically linked to sodium in maintaining osmolality and fluid balance and has an inverse relationship with bicarbonate in maintaining acid-base balance. It is likely because of these close ties that chloride does not get the individual attention it deserves; we can use these facts to simplify and interpret changes in serum chloride concentrations.

Methyl-PEG4-acyl chloride is a PEG-based acylating linker designed for efficient conjugation in targeted protein degradation workflows. Its activated acyl chloride functionality enables rapid formation of stable amide bonds with compatible ligands, while the PEG spacer supports favorable solubility and linker flexibility that can improve PROTAC assembly and performance. The following sections describe the molecule’s structure and practical reactivity considerations in detail.

Structure: The linker comprises a methyl-substituted PEG segment terminated by an acyl chloride. It contains ether linkages within the PEG chain and a reactive carbonyl chloride at the terminus. The combination typically yields a polar, water-compatible scaffold that can enhance solubility and conformational flexibility in PROTAC constructs.

Reactivity: The acyl chloride group readily undergoes nucleophilic acyl substitution with amines to form amides, a common strategy for assembling PROTAC linkers. Reactions are typically performed under anhydrous, inert conditions to minimize hydrolysis, using base to scavenge generated hydrogen chloride. Suitable solvents include polar aprotic media, and coupling is often monitored by consumption of the acyl chloride and appearance of the amide product.

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