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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BCN-PEG4-NHS ester
0 ImagesCat. No.: HY-133439CAS No.: 1702356-19-1
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Azido-PEG1-NHS ester
0 ImagesAzido-PEG1-NHS ester is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG1-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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NH2-PEG6-Boc
0 ImagesNH2-PEG6-Boc is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. NH2-PEG6-Boc is also a non-cleavable 6 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Azido-PEG16-NHS ester
0 ImagesAzido-PEG16-NHS ester is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG16-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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Azido-PEG6-NHS ester
0 ImagesAzido-PEG6-NHS ester is a cleavable 6 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Azido-PEG6-NHS ester is also a PEG- and Alkyl/ether based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG6-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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Mal-PEG12-NHS ester
0 ImagesCat. No.: HY-140963CAS No.: 2669737-09-9
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Fmoc-NH-PEG6-CH2COOH
0 ImagesFmoc-NH-PEG6-CH2COOH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Fmoc-NH-PEG6-CH2COOH is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.
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Bromo-PEG2-C2-Boc
0 ImagesCat. No.: HY-141365CAS No.: 1381861-91-1
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Tetrazine-Ph-PEG5-NHS ester
0 ImagesTetrazine-Ph-PEG5-NHS ester is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Tetrazine-Ph-PEG5-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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Bis-PEG21-NHS ester
0 ImagesBis-PEG21-NHS ester is a PEG/Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs. Bis-PEG21-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Bis-PEG6-NHS ester
0 ImagesBis-PEG6-NHS ester is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. Bis-PEG6-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
