N-(DBCO-PEG4)-N-Biotin-PEG4-NHS
N-(DBCO-PEG4)-N-Biotin-PEG4-NHS is a heterobifunctional PEG-based linker that combines a DBCO (dibenzocyclooctyne) strained-alkyne handle, a biotin affinity tag, and an NHS ester for amide coupling. Structurally, it contains two PEG4 segments that provide aqueous solubility and spacing between functional groups, enabling efficient, low steric hindrance conjugation. In PROTAC and targeted degradation workflows, the DBCO moiety can undergo rapid strain-promoted azide–alkyne cycloaddition to install the linker onto azide-bearing PROTAC components or delivery scaffolds, while the NHS ester allows covalent attachment to primary amines on proteins, peptides, or activated linkers. The biotin group further supports affinity capture, enrichment, and analytical tracking of assembled degraders. This reagent is valuable for constructing modular, well-defined conjugates and for facilitating purification and characterization during iterative PROTAC optimization.
Structure of 2353409-72-8
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This PROTAC linker, N-(DBCO-PEG4)-N-Biotin-PEG4-NHS, integrates a DBCO click handle with orthogonal biotin functionality and an NHS-activated ester for efficient conjugation. Its PEG-based architecture supports aqueous solubility and flexible spacing between binding motifs, which can improve productive ternary complex formation in targeted protein degradation workflows. The sections below describe the structure and practical reactivity considerations for constructing PROTACs using this linker.
Structure: The molecule contains a DBCO moiety for strain-promoted azide–alkyne cycloaddition, two PEG4 spacers that provide hydrophilicity and conformational flexibility, and an NHS ester for acyl transfer. It features amide and ester functionalities and a biotin-derived scaffold enabling strong affinity interactions.
Reactivity: The NHS ester enables coupling to primary amines under mild, aqueous-compatible conditions to form stable amide bonds, typically using buffering near neutral pH and avoiding strong nucleophiles that can hydrolyze the activated ester. The DBCO group reacts via strain-promoted cycloaddition with azide-bearing partners without added catalysts, often in buffered solvents. Biotin-functional conjugates can be assembled or purified using affinity-based approaches, supporting modular PROTAC synthesis.
* 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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