METHOD OF ALTERING POLYPEPTIDE AGGREGATION

摘要

The present invention provides a method of designing a modified polypeptide having an altered tendency to aggregate compared to the unmodified polypeptide. The method comprises: analysing the amino acid sequence of a predetermined polypeptide to determine the propensity of the polypeptide to form local structure; comparing the propensity to form local structure of a modified polypeptide to the propensity to form local structure of an unmodified polypeptide; and determining thereby whether the modified polypeptide has an altered tendency to aggregate in the denatured state relative to the unmodified polypeptide. A selected modified polypeptide having the altered tendency to aggregate is then produced. The invention also provides a method of producing a modified polypeptide having an altered tendency to aggregate compared to the unmodified polypeptide, which method comprises: (i) introducing at least one amino acid modification into a predetermined polypeptide sequence such that said modified polypeptide has an altered propensity to form local structure in the denatured state relative to the unmodified polypeptide, and optionally (ii) recovering the modified polypeptide, and/or optionally (iii) allowing the modified polypeptides to form an aggregate.