N-methyl-N'-methyl-O-(m-PEG4)-O'-(acid-PEG5)-Cy5
N-methyl-N'-methyl-O-(m-PEG4)-O'-(acid-PEG5)-Cy5 is a bifunctional PEG–Cy5 linker designed to couple a near-infrared fluorophore to PROTAC or targeted-degradation constructs through stable ether linkages. Structurally, it comprises a Cy5 chromophore conjugated to a short, branched PEG segment containing an m-PEG4 spacer, followed by an acid-terminated PEG5 region that provides a carboxylic acid handle for further amide or ester coupling to the warhead or E3-ligase–binding moiety. In PROTAC design, this architecture supports flexible, water-soluble tethering that can reduce steric constraints and help maintain productive ternary complex formation while enabling direct fluorescence tracking of compound uptake, intracellular localization, and degradation workflow optimization. Its value lies in facilitating mechanistic studies and assay development for targeted protein degradation by providing a robust imaging tag combined with tunable linker length and a chemically addressable functional group for modular synthesis.
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* For research and manufacturing use only. Not for human or clinical use.
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This N-methylated, PEGylated Cy5 linker is designed to support efficient assembly of PROTAC constructs by providing a flexible, hydrophilic spacer that can reduce steric constraints between a targeting ligand and an E3-recruiting module. The ether-linked PEG segments promote solubility and favorable conformational freedom, while the Cy5 handle enables optical tracking of conjugates during optimization. Detailed structural and reaction guidance are provided below.
Structure: The linker comprises a Cy5 fluorophore connected through ether linkages to two PEG chains, including an m-PEG segment and an acid-PEG segment. N-methylated amine functionality is present, and the structure features ether bonds, PEG ether repeat units, and amide-compatible terminal functionality that supports conjugation chemistry.
Reactivity: Suitable PROTAC assembly typically relies on orthogonal functional-group coupling of the terminal reactive site(s) using standard peptide/amide-forming or activated ester strategies, depending on the complementary warhead chemistries. Reactions are commonly performed under anhydrous or controlled-moisture conditions in polar aprotic solvents, with base or coupling reagents to drive amide bond formation. The PEG ether environment generally tolerates mild conditions and helps maintain solubility during synthesis and purification.
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
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