PEG

N-(NH-Boc-PEG4)-N-bis(PEG4-azide) is a trifunctional linker containing two azides and a Boc-protected primary amine. The azide group is reactive towards terminal alkynes and strained cyclooctynes using click chemistry. The Boc can be removed using acidic conditions to allow the amine to react with carboxylic acids to form stable amide bonds. PEG linkers provide high aqueous solubility, and altering PEG length can alter DMPK.

HO-PEG-Succinimidyl Carbonate, MW 2,000 is a PEG linker containing a succinimidyl carbonate and an alcohol group. The succinimidyl carbonate is a good leaving group that is easily substituted by nucleophiles under mild conditions while the alcohol is a versatile building block that can be applied in a number of ways such as forming esters, ethers, carbonyls and so on.

N-(Azide-PEG8-carbonyl)-N-bis(PEG8-t-butyl ester) is a trifunctional reagent with two t-butyl ester and an azide. The azide group can be used to label terminal alkynes and strained cyclooctynes like BCN or DBCO using click chemistry. The t-butyl esters can be deprotected using acid or base to allow for attack from amines or alcohols. The central junction is a tertiary amide, allowing for hydrogen bonding effects to increase this molecule’s aqueous solubility.

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N-(DBCO)-N-bis(PEG4-Amine) is a trifunctional reagent with two primary amines and a DBCO moiety annealed to a central tertiary amine. The DBCO is a strained cyclooctyne, perfect for labeling azide residues on a target molecule using click chemistry, while the primary amines can be used for reactions with carboxylic acids, aldehydes, or ketones.

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N-(Azide-PEG8-carbonyl)-N-bis(PEG8-acid) is a trifunctional linker combining two carboxylic acids and a terminal azide group. The azide is reactive towards terminal alkynes, BCN or DBCO groups using click chemistry, while the carboxylic acids are free to react with primary amines to form stable amide bonds. This is highly water-soluble PEG linker with altered ADME properties.

N-(Propargyl-PEG4)-PEG4-N-Boc is a bifunctional linker containing a terminal alkyne and a Boc-protected amine. The terminal alkyne is reactive towards azides using copper click chemistry while the NH-Boc group can be deprotected to allow for reactions with carboxylic acids and other carbonyl groups like aldehydes or ketones.

Mal-Amide-PEG4-Val-Cit-PAB-PNP is a cleavable ADC linker which contains a maleimide, a hydrophilic PEG spacer, a valine-citrulline (Val-Cit) dipeptide, a para-aminobenzyl (PAB) spacer and a para-nitrophenyl (PNP) carbonate group. Maleimide is a thiol-specific covalent linker which is used to label cysteine residues in proteins while the PNP carbonate acts as a highly activated leaving group which may be used to react with amines. Val-Cit-PAB linkers are cleaved by cytoplasmic peptidases.