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: C7H13N3O4
- Molecular Weight: 203.20
Azido-PEG2-C2-acid is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG2-C2-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: C12H26N4O5
- Molecular Weight: 306.36
Azido-PEG5-amine is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG5-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: C15H13N5O4
- Molecular Weight: 327.29
Methyltetrazine-Ph-NHS ester is an alkyl/ether-based PROTAC linker that can be used in the synthesis of PROTACs. Methyltetrazine-Ph-NHS ester 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: C8H17N3O4
- Molecular Weight: 219.24
Azido-PEG4-alcohol is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. Azido-PEG4-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: C57H79N11O14S
- Molecular Weight: 1174.38
TAMRA-Azide-PEG-biotin is a dye derivative of TAMRA (HY-135640). TAMRA-Azide-PEG-biotin 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: C43H67N7O9SSi
- Molecular Weight: 886.18
Biotin-PEG4-amino-t-Bu-DADPS-C6-azide is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Biotin-PEG4-amino-t-Bu-DADPS-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: C2H3N3O2
- Molecular Weight: 101.06
Azidoacetic Acid (2-Azidoacetic acid) (compound 92-1) is a click chemistry reagent containing an azide group. Azidoacetic Acid can be used as a small molecule tool for the synthesis of PROTAC. It contains an azide group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing alkyne groups. It can also undergo ring strain-promoted alkyne-azide cycloaddition (SPAAC) with molecules containing DBCO or BCN groups.
- Formula: C36H43N3O11
- Molecular Weight: 693.74
DBCO-PEG5-NHS ester is a PEG/Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs. DBCO-PEG5-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-PEG5-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: C6H12BrN3O2
- Molecular Weight: 238.08
Bromo-PEG2-C2-azide is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Bromo-PEG2-C2-azide is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Bromo-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: C11H21N3O6
- Molecular Weight: 291.30
Azido-PEG4-C2-acid a PEG-based PROTAC linker can be used in the synthesis of vRucaparib-TP4. Azido-PEG4-C2-acid is also a non-cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Azido-PEG4-C2-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: C50H71N3O18
- Molecular Weight: 1002.11
- Formula: C23H40N4O12
- Molecular Weight: 564.58
Azido-PEG8-NHS ester is a cleavable 8 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Azido-PEG8-NHS ester is also a PEG- and Alkyl/ether-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG8-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: C12H18N4O7
- Molecular Weight: 330.29
Azido-PEG3-NHS ester is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-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: C4H10N4O
- Molecular Weight: 130.15
Azido-PEG1-amine is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG1-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: C9H17N3O5
- Molecular Weight: 247.25
N3-PEG3-CH2CH2COOH a PEG-based PROTAC linker can be used in the synthesis of BI-3663 (HY-111546), BI-4216 and BI-0319. Azido-PEG3-acid is also a non-cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). N3-PEG3-CH2CH2COOH 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: C15H29N3O8
- Molecular Weight: 379.41
Azido-PEG6-acid is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG6-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: C42H55N3O14
- Molecular Weight: 825.90
- Formula: C4H10N4
- Molecular Weight: 114.15
4-Azidobutylamine is a PROTAC linker, which refers to the alkyl chain composition. 4-Azidobutylamine can be used in the synthesis of a series of PROTACs. PROTACs contain two different ligands connected by a linker; one is a ligand for an E3 ubiquitin ligase and the other is for the target protein. PROTACs exploit the intracellular ubiquitin-proteasome system to selectively degrade target proteins. 4-Azidobutylamine 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: C22H46N8O8
- Molecular Weight: 550.65
N-(Amino-PEG2)-N-bis(PEG3-azide) is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. N-(Amino-PEG2)-N-bis(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: C8H16BrN3O3
- Molecular Weight: 282.13
Bromo-PEG4-azide is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Bromo-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.
