Alkyl/ether Linkers
Alkyl/ether linkers are widely used molecular spacers in chemical biology, medicinal chemistry, antibody-drug conjugates (ADCs), and proteolysis-targeting chimeras (PROTACs), where they connect functional ligands while modulating physicochemical and biological properties of the resulting molecules[1][2]. Mechanistically, linker composition influences molecular flexibility, spatial orientation, and effective distance between functional domains, thereby affecting target engagement, ternary-complex formation, and overall biological activity[1][2]. Among commonly used linker classes, alkyl chains and polyethylene glycol (PEG)-derived ether linkers have dominated linker design because they are synthetically accessible, flexible, and readily tuned in length[1][3]. Ether-containing PEG linkers introduce polarity and hydrogen-bond-accepting oxygen atoms that can improve aqueous solubility and biocompatibility, making them valuable for conjugation and drug-delivery applications[1][4]. In contrast, alkyl linkers provide a more hydrophobic scaffold with fewer heteroatoms, which can enhance membrane permeability and alter pharmacokinetic behavior in cellular systems[1][2]. Compared with PEG-based ether linkers, alkyl linkers generally contribute lower polarity, whereas PEG-containing linkers offer greater hydrophilicity and broader opportunities for tuning solubility-related properties[1][4]. Therefore, the choice between alkyl and ether linker architectures is frequently guided by the balance required among molecular flexibility, polarity, permeability, and application-specific performance[1][2][3]. For experimental applications, systematic variation of linker length and composition remains a common strategy for optimizing molecular recognition, intracellular activity, and structure-activity relationships during compound development[1][2].
References:
- [1]. Troup RI, et al. Current strategies for the design of PROTAC linkers: a critical review. Explor Target Antitumor Ther. 2020;1(5):273-312. [Content Brief]
- [2]. Dong Y, et al. Characteristic roadmap of linker governs the rational design of PROTACs. Acta Pharm Sin B. 2024 Oct;14(10):4266-4295. [Content Brief]
- [3]. Wikipedia.
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Alkyl/ether Linkers Related Products (493)
Related Products (493)
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m-PEG11-NHS ester
0 ImagesCat. No.: HY-141105CAS No.: 3119903-67-9
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N-(Azido-PEG2)-N-Boc-PEG3-NHS ester
0 ImagesCat. No.: HY-140559CAS No.: 2093153-85-4N-(Azido-PEG2)-N-Boc-PEG3-NHS ester is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. N-(Azido-PEG2)-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.
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Bromoacetamido-PEG2-C2-NHS ester
0 ImagesCat. No.: HY-141386CAS No.: 1353011-78-5
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Propargyl-PEG6-NHS ester
0 ImagesPropargyl-PEG6-NHS ester is a PEG/Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs. Propargyl-PEG6-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Propargyl-PEG6-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.
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Azido-PEG12-NHS ester
0 ImagesAzido-PEG12-NHS ester is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG12-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.
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Tetrazine-Ph-NHS ester
0 ImagesCat. No.: HY-126908CAS No.: 1616668-55-3Tetrazine-Ph-NHS ester is an alkyl/ether-based PROTAC linker that can be used in the synthesis of PROTACs. Tetrazine-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.
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Hydroxy-PEG4-C2-methyl ester
0 ImagesCat. No.: HY-141242CAS No.: 2228857-35-8
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tert-Butyl 11-aminoundecanoate
0 Imagestert-Butyl 11-aminoundecanoate (compound 6b) is a PROTAC linker, which refers to the PEG composition. tert-Butyl 11-aminoundecanoate 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.
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Bromoacetamido-PEG3-C2-Boc
0 ImagesCat. No.: HY-141388CAS No.: 1807537-33-2
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Fmoc-NH-PEG5-CH2COOH
0 ImagesCat. No.: HY-133062CAS No.: 635287-26-2Fmoc-NH-PEG5-CH2COOH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Fmoc-NH-PEG5-CH2COOH is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.
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t-Boc-Aminooxy-PEG2-azide
0 ImagesCat. No.: HY-140431CAS No.: 252378-68-0t-Boc-Aminooxy-PEG2-azide is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. t-Boc-Aminooxy-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.
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Bromo-PEG2-CH2-Boc
0 ImagesCat. No.: HY-141371CAS No.: 1807518-63-3
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Azido-PEG4-CH2-Boc
0 ImagesCat. No.: HY-42618CAS No.: 864681-04-9Azido-PEG4-CH2-Boc is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Azido-PEG4-CH2-Boc is also a PEG- and Alkyl/ether-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG4-CH2-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.
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Hydroxy-PEG2-C2-PFP ester
0 ImagesCat. No.: HY-130488CAS No.: 1820673-42-4
