N-Desthiobiotin-N-bis(PEG4-NHS ester)
N-Desthiobiotin-N-bis(PEG4-NHS ester) is a heterobifunctional PEG-based linker that combines a desthiobiotin affinity handle with two terminal N-hydroxysuccinimide (NHS) ester groups. Structurally, it features a desthiobiotin moiety for reversible binding to streptavidin or streptavidin-like proteins, connected through a flexible PEG4 spacer to each NHS-activated end, enabling amide-bond formation with primary amines on proteins, peptides, or other amine-bearing PROTAC components. In PROTAC design and targeted degradation workflows, this linker is used to conjugate a biotin-recognizing module to an amine-functionalized ligand or scaffold, while the dual NHS esters provide controlled, stoichiometric attachment sites that can increase conjugation efficiency and tune effective linker length and flexibility. Its value lies in facilitating modular assembly, enabling affinity-guided purification or immobilization, and supporting systematic optimization of conjugate architecture for studying ternary complex formation and degradation potency in targeted protein degradation research.
Structure of 2353409-61-5
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N-Desthiobiotin-N-bis(PEG4-NHS ester), is designed to connect biotin-based targeting motifs to amine-reactive handles for efficient conjugation in targeted protein degradation workflows. Its PEG-rich architecture supports solubility and flexible spacing, while the desthiobiotin element enables affinity-based capture and enrichment strategies. The molecule’s dual NHS ester functionality facilitates the assembly of multifunctional degraders, and the detailed structural and reactivity characteristics are described below.
Structure: The linker contains a desthiobiotin core and two PEG4 arms terminating in N-hydroxysuccinimide (NHS) ester groups. It features stable amide-forming acyl linkages potential, ether-rich PEG segments, and electrophilic NHS-activated carbonyls. These traits promote water compatibility and conformational flexibility for PROTAC conjugation.
Reactivity: The NHS esters undergo nucleophilic acyl substitution with primary amines to form stable amide bonds, a common strategy for building PROTACs from lysine- or amine-functionalized ligands. Typical coupling is performed under mildly basic aqueous buffer conditions that preserve NHS reactivity, using freshly prepared solutions and controlled stoichiometry. No special catalysts are required; reaction progress is monitored by standard conjugation analytics, and unreacted NHS esters are quenched after coupling.
* 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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