Glutathione (GSH) is the most abundant tripeptide in human cells and plays an important role in protecting cells' integrity against oxidative stress. GSH has an unusual amide linkage formed between the gamma-carboxylic group of the glutamic acid in its side-chain and the amine group of cysteine residue. In the present study, we have compared reactivities of GSH to its isomer GluCysGly (ECG), which has a regular amide bond formed between the alpha-carboxylic group of glutamic acid and the amine group of cysteine residue. The fragmentation pattern of GSH ions in the gas phase is different from that of ECG ions, showing that the loss of H2O is the major dissociation pathway in ECG fragmentation. This is consistent with the dissociation pathway predicted by density functional calculation. Formation of GSSG from oxidation of GSH is faster than that of ECG disulfide, and the gas phase fragmentation pattern of GSSG is different from that of ECG disulfide. GSH and ECG display similar rates in nudeophilic aromatic substitution when reacting with 1-chloro-2,4-dinitrobenzene (CDNB). However, in the presence of glutathione S-transferases (GST), substitution of CDNB by GSH is 10 times faster than that by ECG. GSH and ECG also show differences in clustering patterns in the gas phase. Taken together, our results shed light on understanding effects of unique boding structure in GSH on its stability and reactivities.