Abstract: The present invention relates to the targeting and clearance of soluable unprocessed Islet Amyloid Polypeptide (hIAPP) in order to prevent the nucleation of hIAPP amyloidogenesis and to interfere with pancreatic cell death which is associated with the aggregation of hIAPP. Agents and methods for reducing hIAPP aggregation are provided herein and may be useful in the treatment of type 2 diabetes.

Abstract: A prediction method for predicting the effect of an amino acid modification on the rate of aggregation (solubility) of a reference polypeptide comprising: calculating the difference in hydrophobicity (?Hydr) between the reference polypeptide and a modified polypeptide, calculating the difference in ?-sheet propensity (??Gcoil-?+??G?-coil) between the reference polypeptide and modified polypeptide, calculating the difference in charge (?Charge) between the reference polypeptide and modified polypeptide, and calculating: [x*?Hydr]+[y*(??Gcoil-?+??G?-coil)]?[z*?Charge], wherein x, y and z are scaling factors.

Abstract: A prediction method for predicting the effect of an amino acid modification on the rate of aggregation (solubility) of a reference polypeptide comprising: calculating the difference in hydrophobicity (?Hydr) between the reference polypeptide and a modified polypeptide, calculating the difference in ?-sheet propensity (??Gcoil-?+??G?-coil) between the reference polypeptide and modified polypeptide, calculating the difference in charge (? Charge) between the reference polypeptide and modified polypeptide, and calculating: [x*?Hydr]+[y*(??Gcoil-?+??G?-coil)]?[z*? Charge], wherein x, y and z are scaling factors.

Abstract: A method of determining aggregation rate data predicting an aggregation rate of a polypeptide defined by an amino acid sequence, the method comprising determining a hydrophobicity value, a charge value, and at least one shape propensity value for said sequence; identifying one or more aggregation-influencing patterns within said sequence; determining a pattern value for the sequence responsive to said identifying; and determining said aggregation rate data by determining a weighted combination of said hydrophobicity value, said charge value, said at least one shape propensity value, said pattern value and at least one factor extrinsic to said amino acid sequence.

Abstract: A prediction method for predicting the effect of an amino acid modification on the rate of aggregation (solubility) of a reference polypeptide comprising: calculating the difference in hydrophobicity (?Hydr) between the reference polypeptide and a modified polypeptide, calculating the difference in ?-sheet propensity (??Gcoil-?+??G?-coil) between the reference polypeptide and modified polypeptide, calculating the difference in charge (? Charge) between the reference polypeptide and modified polypeptide, and calculating: [x*?Hydr]+[y*(??Gcoil-?+??G?-coil)]?[z*? Charge], wherein x, y and z are scaling factors.

Abstract: A method of purifying amyloid fibrils comprises treating a sample containing the fibris with a protease, detergent, chemical denatuarant or chaotrope. The amyloid fibrils may then be collected from the treated sample. The treatment is preferably carried out under conditions which allow digestion, degradation or denaturation of amorphous aggregates and soluble precursors in the sample but which do not digest, degrade or denature the amyloid fibrils. A homogonous preparation of amyloid fibrils is provided in which fibrils comprise at least 80% by weight of protein in the sample.

Abstract: Bioactive peptides are modified to have an increased solubility or reduced tendency to aggregate compared to the wild type modified peptide. In particular modified human calcitonin comprises a peptide having at least 70% identity to SEQ ID NO: 1 and being modified such that the tendency of the modified peptide to aggregate is reduced compared to unmodified human calcitonin.