Orthopyridyl disulfide (OPSS) PEGs are thiol-specific PEGylation reagents that react with free sulfhydryls (-SH) at a wide pH range (pH 3-10) through disulfide exchange. The newly formed disulfide (S-S) bond is unstable in a reducing environment. Thus, the bond can be cleaved to reverse the pegylation and release free thiols. PEG-NHS ester derivatives are active esters and useful reagents to pegylate proteines, peptides or any other surfaces with a free primary amino group to form stable amide bonds. The Reaction requires a neutral to alkaline pH (7 to 8.5) to proceed. However, hydrolysis competes with aminolysis of the active ester and also increases with higher pH. Thus, working with excess PEG-NHS ester is necessary to obtain high pegylation yields. The PEG butyric acid NHS ester derivative has a C4 chain directly attached to PEG. It is one of the most stable PEG NHS esters known with a hydrolysis half-life of over 20 min at pH 8.