PEGs with an active ester functional group at one end allow for selective and covalent attachment to other molecules with complementary functional groups, such as primary amines on proteins, peptides, or other molecules. To a lesser extent they are reactive towards thiols or hydroxyls (to form thioesters or esters) . Squaric Acid Ester Amido PEGs are a novel class of reactive and chemoselective PEG crosslinking reagents. The squaric acid PEGs are chemoselective towards the amino groups of Lysin in protein PEGylation whereas the guanidine function of Arginine, the hydroxyl group of Serine and the imidazole function of Histidine are not affected. Compared to other active esters, these PEGs are remarkably stable in aqueous media and not easily hydrolyzed. The biotinyl functionality is used to attach avidin or streptavidin containing substrates. Pegylation by binding of biotinyl PEG to avidin and streptavidin is very specific and fast.