ACID-CATALYZED PEPTIDE-BOND HYDROLYSIS OF RECOMBINANT HUMAN INTERLEUKIN-11

Recombinant human interleukin 11(rhIL-11) is a multispectrum cytokine that plays an important role in megakaryocytopoiesis and platelet prod uction. Probing rhIL-11 chemical reactivity in aqueous solution is an important initial step in developing a dosage form for rhIL-11 clinica l trials. This report documents rhIL-11 degradation kinetics at 50-deg rees-C in solutions adjusted to pH 3.0 to 9.5. Stressed samples were a nalyzed by reverse-phase HPLC and degradation product peaks were isola ted for structural characterization. The results show maximal stabilit y in the region pH 6.5 to 7.0. Degradation product identification show s that the major reaction pathway in acidic solution involves peptide cleavage at aspartate33-proline134. In alkaline solution, protein disa ppearance proceeds via nonspecific loss to container surfaces. Degrada tion products at alkaline pH have not been identified.