PROTAC Synthesis
PROTAC molecules are generally composed of three parts: ligand for target protein, linker and ligand for E3 ligase. “Click chemistry” reactions provide an accessible and tunable strategy for the selection of synthetic linkers and lay a solid foundation for the development of a diverse library of PROTACs in biomedical research. The copper-catalyzed reaction is typically high yielding, requiring stoichiometric quantities of each component and boasts excellent functional group compatibility under mild reaction conditions. This approach would allow for the parallel synthesis of libraries of PROTACs provided the necessary azides and alkynes could be prepared. For example, click chemistry was utilized to prepare a library of PROTACs based on entinostat a class I histone deacetylase (HDAC) inhibitor in clinical trials. Recently, an advanced PROTAC technology was developed, namely CLIPTAC (in-cell click-formed proteolysis-targeting chimeras), with two precursor components combined by bioorthogonal “click” reaction.
- Formula: C4H9N3O2
- Molecular Weight: 131.13
Azido-PEG2-alcohol is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG2-alcohol is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.
- Formula: C33H38N6O7
- Molecular Weight: 630.69
TAMRA-PEG3-Azide is a dye derivative of TAMRA (HY-135640) containing 3 PEG units. TAMRA-PEG3-Azide contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.
- Formula: C17H28N4O9
- Molecular Weight: 432.43
Azido-PEG5-NHS ester is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG5-NHS ester is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.
- Formula: C26H37N3O8
- Molecular Weight: 519.59
- Formula: C28H52N8O12
- Molecular Weight: 692.76
DOTA-PEG5-azide is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. DOTA-PEG5-azide is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.
- Formula: C16H28N6O4S
- Molecular Weight: 400.50
Biotin-PEG2-azide is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. Biotin-PEG2-azide is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.
- Formula: C27H49N7O7S
- Molecular Weight: 615.79
Biotin-PEG4-Amide-C6-Azide is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Biotin-PEG4-Amide-C6-Azide is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.
- Formula: C27H42N8O7S
- Molecular Weight: 622.74
Biotin-PEG4-Picolyl azide is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Biotin-PEG4-Picolyl azide is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.
- Formula: C55H104N4O28
- Molecular Weight: 1269.42
Azido-PEG24-NHS ester is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG24-NHS ester is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.
- Formula: C6H13N3O3
- Molecular Weight: 175.19
Azido-PEG3-alcohol is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. Azido-PEG3-alcohol is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.
- Formula: C6H11N3O4
- Molecular Weight: 189.17
Azido-PEG2-CH2COOH is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. Azido-PEG2-CH2COOH is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.
- Formula: C18H34N6O5
- Molecular Weight: 414.50
Azide-PEG3-Desthiobiotin is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azide-PEG3-Desthiobiotin is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.
- Formula: C25H51N3O12
- Molecular Weight: 585.69
m-PEG12-azide is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. m-PEG12-azide is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.
- Formula: C18H26N2O7
- Molecular Weight: 382.41
- Formula: C14H30N4O6
- Molecular Weight: 350.41
Azido-PEG6-amine is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG6-amine is also a non-cleavable 6 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Azido-PEG6-amine is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.
- Formula: C10H21N3O5
- Molecular Weight: 263.29
Azido-PEG5-alcohol is a non-cleavable 5 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Azido-PEG5-alcohol is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG5-alcohol is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.
- Formula: C16H34N4O7
- Molecular Weight: 394.46
Azido-PEG7-amine is a non-cleavable 7 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Azido-PEG7-amine is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG7-amine is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.
- Formula: C24H30N6O7
- Molecular Weight: 514.53
Methyltetrazine-PEG4-maleimide is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Methyltetrazine-PEG4-maleimide is a click chemistry reagent, it contains a Tetrazine group that can undergo an inverse electron demand Diels-Alder reaction (iEDDA) with molecules containing TCO groups.
- Formula: C7H13NO2
- Molecular Weight: 143.18
Propargyl-PEG2-amine is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Propargyl-PEG2-amine is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. Propargyl-PEG2-amine is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
- Formula: C22H46N4O10
- Molecular Weight: 526.62
Azido-PEG10-amine is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG10-amine is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.
