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: C11H22N4O4
- Molecular Weight: 274.32
Boc-N-Amido-PEG2-C2-azide is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Boc-N-Amido-PEG2-C2-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: C19H31N3O8S
- Molecular Weight: 461.53
Azide-PEG6-Tos is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azide-PEG6-Tos 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: C13H26N4O5
- Molecular Weight: 318.37
Boc-N-Amido-PEG3-azide is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Boc-N-Amido-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: C15H26O6
- Molecular Weight: 302.36
- Formula: C54H74N6O16S
- Molecular Weight: 1095.26
N-(DBCO-PEG4)-N-Biotin-PEG4-NHS is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. N-(DBCO-PEG4)-N-Biotin-PEG4-NHS 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: C24H46N4O9
- Molecular Weight: 534.64
N-(Azido-PEG2)-N-Boc-PEG3-Boc is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. N-(Azido-PEG2)-N-Boc-PEG3-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: C40H78N4O16
- Molecular Weight: 871.06
N-(Azido-PEG4)-N-bis(PEG4-t-butyl ester) is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. N-(Azido-PEG4)-N-bis(PEG4-t-butyl 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: C25H29N3O4
- Molecular Weight: 435.52
- Formula: C18H38N4O7Si
- Molecular Weight: 450.60
Azido-PEG3-amide-C3-triethoxysilane is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG3-amide-C3-triethoxysilane 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: C25H49N7O10
- Molecular Weight: 607.70
N-Boc-N-bis(PEG4-azide) is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. N-Boc-N-bis(PEG4-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: C11H20N4O4
- Molecular Weight: 272.30
Azido-PEG4-nitrile is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG4-nitrile 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: C17H34N4O8
- Molecular Weight: 422.47
N-(Azido-PEG3)-NH-PEG3-acid is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. N-(Azido-PEG3)-NH-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: C18H23NO9
- Molecular Weight: 397.38
Propargyl-PEG4-5-nitrophenyl carbonate is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Propargyl-PEG4-5-nitrophenyl carbonate 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: C24H26F5NO6
- Molecular Weight: 519.46
- Formula: C14H24O5
- Molecular Weight: 272.34
- Formula: C26H50N4O10
- Molecular Weight: 578.70
N-(Azido-PEG3)-N-Boc-PEG3-t-butyl ester is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. N-(Azido-PEG3)-N-Boc-PEG3-t-butyl 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: C26H45N5O12
- Molecular Weight: 619.66
N-(Azido-PEG3)-N-Boc-PEG3-NHS ester is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. N-(Azido-PEG3)-N-Boc-PEG3-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: C8H17N7O2
- Molecular Weight: 243.27
NH-bis(C2-PEG1-azide) is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. NH-bis(C2-PEG1-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: C16H27NO5
- Molecular Weight: 313.39
Hydroxy-Amino-bis(PEG2-propargyl) is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Hydroxy-Amino-bis(PEG2-propargyl) 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: C15H29NO6
- Molecular Weight: 319.39
