3,6,9,12,15-Pentaoxaoctadec-17-ynoic acid
3,6,9,12,15-Pentaoxaoctadec-17-ynoic acid is a PEG-like, ether-rich alkyne-containing linker acid featuring five internal ethylene-oxide units that provide conformational flexibility and improved aqueous compatibility, together with a terminal carboxylic acid for controlled conjugation. The alkyne functionality enables orthogonal chemical handles for subsequent coupling strategies (e.g., click-type or other alkyne-compatible chemistries), while the extended ether chain acts as a spacer to reduce steric interference between a targeting ligand and an E3-recruiting moiety in PROTAC constructs. In targeted protein degradation design, such flexible, oxygenated linkers are commonly used to tune effective reach, maintain productive ternary complex formation, and mitigate unfavorable intramolecular contacts that can lower degradation efficiency. As a modular linker building block, this acid supports systematic optimization of linker length and polarity, facilitating structure–activity relationship studies in PROTAC synthesis and enabling reproducible preparation of degraders for mechanistic and cellular evaluation.
Structure of 1429934-37-1
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* For research and manufacturing use only. Not for human or clinical use.
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This PROTAC linker, 3,6,9,12,15-Pentaoxaoctadec-17-ynoic acid, provides a polyethylene-oxide–like, flexible spacing element that can be incorporated into targeted protein degradation constructs to tune linker length, solvation, and ternary-complex formation. Its terminal carboxylic acid enables robust conjugation strategies to install warheads and E3 ligase-binding ligands. The detailed structural and synthetic considerations are provided below.
Structure: The molecule is an alkyne-containing, ether-rich chain featuring multiple internal oxygen atoms that impart conformational flexibility and polarity. A terminal carboxylic acid provides a chemically defined functional handle for amide or ester formation, while the carbon–carbon triple bond offers a stable, non-oxidizing linkage point under typical coupling conditions.
Reactivity: The carboxylic acid is well suited for standard PROTAC linker coupling via amide bond formation using activated carboxyl derivatives (for example, acid chlorides or carbodiimide-mediated activation) with amine-bearing partners. Typical conditions employ polar aprotic solvents and base to promote condensation. The alkyne generally tolerates these transformations without requiring specialized catalysts, enabling sequential assembly of bifunctional PROTAC intermediates under controlled, anhydrous handling.
* 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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