Susceptibility of rhDNase I to glycation in the dry-powder state.

The accumulated data on the glycation process in rhDNase I, formulated with lactose and stored in the dry-powder state, indicates that this protein becomes covalently modified with lactose at five of the six lysines (2, 50, 77, 157, 260) and to a lesser extent on the amino terminus. Analysis of the three-dimensional protein structure indicates that the reported requirements for the specificity of site reactivity, site accessibility, and the presence of a proton donor/acceptor group near the reaction site, are maintained in this protein. A chemical reaction in the dry-powder state may become permissible simply due to the close packing and resultant high concentrations of the reactant molecules. The reaction between reducing sugar and protein in the dried state indicates that the arrangement of molecules within the dry-powder particle allows for direct contact between all the reactants, including contacts between protein molecules, which may contribute to the completion of the covalent reaction at a surface...