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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Tos-O-C4-NH-Boc
0 ImagesCat. No.: HY-132004CAS No.: 180851-50-7Tos-O-C4-NH-Boc is an alkyl ether-based PROTAC linker can be used in the synthesis of PROTACs, such as BSJ-03-204 (HY-136250).
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9-Decyn-1-ol
0 ImagesCat. No.: HY-130985CAS No.: 17643-36-69-Decyn-1-ol is an alkyl/ether-based PROTAC linker that can be used in the synthesis of PROTACs. 9-Decyn-1-ol can be used to conjugate GDC-0068 with Lenalidomide to generate INY-03-041. INY-03-041 is a potent, highly selective and PROTAC-based pan-Akt degrader. INY-03-041 inhibits Akt1, Akt2 and Akt3 with IC50s of 2.0 nM, 6.8 nM and 3.5 nM, respectively. 9-Decyn-1-ol 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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Bromo-PEG6-Boc
0 ImagesCat. No.: HY-141367CAS No.: 1393330-41-0
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3,4-Dibromo-Mal-PEG2-N-Boc
0 ImagesCat. No.: HY-141005CAS No.: 1807537-43-4
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Ms-PEG2-C2-Boc
0 ImagesCat. No.: HY-140383CAS No.: 1312309-62-8
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Azido-PEG4-Boc
0 ImagesCat. No.: HY-140777CAS No.: 581066-04-8Azido-PEG4-Boc is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG4-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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NH-bis(PEG2-C2-Boc)
0 ImagesCat. No.: HY-140256CAS No.: 1964503-36-3
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Azido-PEG9-NHS ester
0 ImagesAzido-PEG9-NHS ester is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG9-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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m-PEG13-NHS ester
0 ImagesCat. No.: HY-141107CAS No.: 3063847-98-0
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Fmoc-PEG5-NHS ester
0 ImagesCat. No.: HY-122459CAS No.: 1402080-11-8
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DBCO-NHCO-PEG4-NH-Boc
0 ImagesCat. No.: HY-126884CAS No.: 1255942-12-1DBCO-NHCO-PEG4-NH-Boc is a PEG/Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs. DBCO-NHCO-PEG4-NH-Boc is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-NHCO-PEG4-NH-Boc is a click chemistry reagent, it contains a DBCO group that can undergo strain-promoted alkyne-azide cycloaddition (SPAAC) with molecules containing Azide groups.
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N3-PEG3-CH2CH2-Boc
0 ImagesCat. No.: HY-42489CAS No.: 252881-73-5N3-PEG3-CH2CH2-Boc is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). N3-PEG3-CH2CH2-Boc is also a PEG- and Alkyl/ether-based PROTAC linker that can be used in the synthesis of PROTACs. N3-PEG3-CH2CH2-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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Fmoc-PEG2-C2-NHS ester
0 ImagesCat. No.: HY-126881CAS No.: 1807534-85-5
