Experimental Inhibition of Peptide Fibrillogenesis by Synthetic Peptides, Carbohydrates and Drugs

Abstract

Peptide fibrillogenesis generally begins by the transformation of normally soluble proteins into elongated aggregates which are called as amyloid. These fibrils mainly consist of ß-sheets. They share certain common characteristics such as a cross-ß x-ray diffraction pattern, association with other common proteins and typical staining by the dye Congo Red. The individual form of the deposit consists of a disease-specific peptide/protein. The disease-specific protein serves as the basis for the classification of the amyloids. The association of fibril-forming peptides/proteins with diseases makes them primary disease-targets. Understanding the molecular interactions involved in the fibril formation becomes the foremost requirement to characterize the target. Interference with these interactions of ß-sheets in vitro prevents and sometimes reverses the fibril assembly. A small molecule capable of interfering with the formation of fibril could have therapeutic applications in these diseases. This anti-aggregation approach appears to be a viable treatment option. A search for such a molecule is pursued actively world over. All types of compounds and approaches to slow down or prevent the aggregation process have been described in the literature. These efforts are reviewed in this chapter.