Acid-PEG5-NHS ester
Acid-PEG5-NHS ester is a heterobifunctional polyethylene glycol (PEG) linker featuring one free carboxylic acid terminus and one N-hydroxysuccinimide (NHS) ester terminus, enabling efficient amide-bond formation with primary amines on target-binding ligands (e.g., lysine-bearing peptides or amine-functionalized small molecules). Structurally, it provides a flexible PEG chain of moderate length that can improve aqueous solubility, reduce nonspecific hydrophobic interactions, and help spatially separate the conjugated warhead from the recruited-ligand moiety in PROTAC constructs. In targeted protein degradation design, the NHS ester reacts with an amine-containing component while the free acid remains available for separate activation and coupling, yielding stable amide linkages that preserve the geometry required for ternary complex formation. Its value lies in providing a robust, chemoselective conjugation handle that facilitates modular PROTAC synthesis and optimization of linker length and flexibility to tune degradation efficiency and selectivity.
Structure of 1343476-41-4
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Acid-PEG5-NHS ester is a polyethylene glycol (PEG)-based linker designed for efficient conjugation in targeted protein degradation workflows. Its activated N-hydroxysuccinimide (NHS) ester enables rapid formation of stable amide bonds with primary amine groups, supporting the modular assembly of PROTACs and related bifunctional degraders. The PEG spacer can improve solubility and provide conformational flexibility, which may help maintain productive geometry between ligand domains. Detailed structural and reactivity considerations are provided below.
Structure: Acid-PEG5-NHS ester contains a PEG chain terminated by a carboxylic acid and an NHS-activated ester. It features ester and amide-forming functional groups, with ether linkages along the PEG backbone. The molecule is typically water-compatible and shows enhanced hydrophilicity due to the PEG segment.
Reactivity: The NHS ester reacts with primary amines to form amide bonds under mildly basic aqueous or mixed solvent conditions, commonly using buffering systems that preserve NHS reactivity. The mechanism involves nucleophilic attack by the amine on the activated carbonyl, followed by NHS leaving-group departure. No special catalysts are generally required; careful control of pH and avoidance of competing nucleophiles are important.
* 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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