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: C17H35N3O8
- Molecular Weight: 409.48
m-PEG8-azide is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. m-PEG8-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: C11H23N3O5
- Molecular Weight: 277.32
m-PEG5-azide is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. m-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: C24H46N4O11
- Molecular Weight: 566.64
N-(Azido-PEG3)-N-Boc-PEG4-acid is a PEG-based PROTAC linker with a terminal azide group and is used in the synthesis of PROTACs N-(Azido-PEG3)-N-Boc-PEG4-acid 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: C22H36N4O5S
- Molecular Weight: 468.61
- Formula: C23H45NO10
- Molecular Weight: 495.60
- Formula: C24H42O10
- Molecular Weight: 490.58
Bis-propargyl-PEG9 is a PEG-based PROTAC linker used in the synthesis of PROTACs. Bis-propargyl-PEG9 can be used to synthesize the bivalent estrogen receptor ligands. Bis-propargyl-PEG9 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: C38H45N5O13S
- Molecular Weight: 811.85
N-(Azido-PEG3)-N-Fluorescein-PEG3-acid is a PEG-based PROTAC linker which contains azide, fluorescein and carboxylic acid moieties. N-(Azido-PEG3)-N-Fluorescein-PEG3-acid 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: C23H45N3O10
- Molecular Weight: 523.62
Azido-PEG8-Boc is a PEG- and Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs. Azido-PEG8-Boc 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: C18H22F5N3O7
- Molecular Weight: 487.38
Azido-PEG5-CH2CO2-PFP is a PEG- and Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs. Azido-PEG5-CH2CO2-PFP 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: C21H39BrO9
- Molecular Weight: 515.43
Propargyl-PEG9-bromide is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. Propargyl-PEG9-bromide is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Propargyl-PEG9-bromide 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: C18H35N3O10
- Molecular Weight: 453.48
N3-PEG8-CH2COOH is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. N3-PEG8-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: C18H30O7
- Molecular Weight: 358.43
Bis-propargyl-PEG6 is a PEG-based PROTAC linker used in the synthesis of PROTACs. Bis-propargyl-PEG6 can be used to synthesize the polymer linked multimers of guanosine-3', 5'-cyclic monophosphates. Bis-propargyl-PEG6 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: C22H35NO11
- Molecular Weight: 489.51
Propargyl-PEG7-NHS ester is a PEG/Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs. Propargyl-PEG7-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Propargyl-PEG7-NHS ester 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: C10H14O3
- Molecular Weight: 182.22
Bis-propargyl-PEG2 is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. Bis-propargyl-PEG2 is used for the synthesis of demethylvancomycin dimers. Bis-propargyl-PEG2 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: C16H22N4O5
- Molecular Weight: 350.37
Ald-Ph-amido-C2-PEG3-azide is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Ald-Ph-amido-C2-PEG3-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: C34H39N3O10
- Molecular Weight: 649.69
DBCO-NHCO-PEG4-NHS ester is a PEG/Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs. DBCO-NHCO-PEG4-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-NHCO-PEG4-NHS ester is a click chemistry reagent, it contains a DBCO group that can undergo strain-promoted alkyne-azide cycloaddition (SPAAC) with molecules containing Azide groups.
- Formula: C18H32O7
- Molecular Weight: 360.44
Propargyl-PEG4-CH2CH2-Boc is a non-cleavable ADC linker that can be used to synthesize ADC inhibitors of Galectin-3. Propargyl-PEG4-CH2CH2-Boc is a PEG- and Alkyl/ether-based PROTAC linker that can be used in the synthesis of PROTACs. Propargyl-PEG4-CH2CH2-Boc 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: C32H40N2O9
- Molecular Weight: 596.67
DBCO-Amide-PEG5-acid is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. DBCO-Amide-PEG5-acid is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-NHCO-PEG4-acid is a click chemistry reagent, it contains a DBCO group that can undergo strain-promoted alkyne-azide cycloaddition (SPAAC) with molecules containing Azide groups.
- Formula: C17H25NO9
- Molecular Weight: 387.38
Propargyl-PEG4-O-C1-NHS ester (compound 8) is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. Propargyl-PEG4-O-C1-NHS ester 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: C22H38O9
- Molecular Weight: 446.53
