Theoretical study on pegylation reaction mechanisms of IFN-α-2a, IFN-α-2b and IFN-β-1a

Ab initio and DFT calculations have been carried out to study the reaction mechanism between interferons (IFNs) α-2a, α-2b and β-1a and polyethylene glycol (PEG) group. The calculations show that the mechanisms are concerted, in agreement with the results of experimental works. However, although it appears that there is one single transition state, the characteristics of its structure reveal a very synchronous reaction mechanism. The reactions are clearly exothermic and as well have feasible activation energies. Our computational study shows that the lowest transition state energies are related to Lys 134, His 34 and Met 1 of IFN-α-2a, IFN-α-2b and IFN-β-1a, respectively