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 production. Probing rhIL-11 chemical reactivity in aqueous solution is an important initial step in developing a dosage form for rhIL-11 clinical trials. This report documents rhIL-11 degradation kinetics at 50 degrees C in solutions adjusted to pH 3.0 to 9.5. Stressed samples were analyzed by reverse-phase HPLC and degradation product peaks were isolated for structural characterization. The results show maximal stability in the region pH 6.5 to 7.0. Degradation product identification shows that the major reaction pathway in acidic solution involves peptide cleavage at aspartate133-proline134. In alkaline solution, protein disappearance proceeds via nonspecific loss to container surfaces. Degradation products at alkaline pH have not been identified.
Kenley
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RA
Genetics Institute, Andover, Massachusetts 01810.
Warne
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NW
D000143:Acids; D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D017370:Interleukin-11 / Q000737:chemistry*; D007700:Kinetics; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry
D000143:Acids; D017370:Interleukin-11; D010455:Peptides; D011994:Recombinant Proteins