The effect of compactional pressure on urease activity.

Jack bean urease is a proteinaceous enzyme, MW approximately 489 kD, readily soluble in water but losing activity when sheared in solution at stresses as low as 2.5 Pa. There is a need for controlled-release forms of many of the new genetically engineered peptide and polypeptide drugs with high specific activities. The simplest form of controlled release would be a sterile compressed pellet of the active component inserted subdermally. However, "activity" may be lost on compaction. Urease can be regarded as a model protein which may lose activity when sheared during compaction in the dry state. Tablets of urease weighing 100 mg were compressed over a range of pressures from 60 to 1750 MPa. No relative loss of activity would be detected following compaction at pressures up to 474 MPa. Above this limiting pressure there was a 50% loss of relative activity, evidently by a compactional effect on the protein quaternary and tertiary structures. No direct relationship was observed between stress (compactional pressure) and inactivation.