Tissue transglutaminase-mediated glutamine deamidation of beta-amyloid peptide increases peptide solubility, whereas enzymatic cross-linking and peptide fragmentation may serve as molecular triggers for rapid peptide aggregation.

Tissue transglutaminase (TGase) has been implicated in a number of cellular processes and disease states, where the enzymatic actions of TGase may serve in both, cell survival and apoptosis. To date, the precise functional properties of TGase in cell survival or cell death mechanisms still remain elusive. TGase-mediated cross-linking has been reported to account for the formation of insoluble lesions in conformational diseases.

Switch-peptides: design and characterization of controllable super-amyloid-forming host-guest peptides as tools for identifying anti-amyloid agents.

Several amyloid-forming proteins are characterized by the presence of hydrophobic and highly amyloidogenic core sequences that play critical roles in the initiation and progression of amyloid fibril formation. Therefore targeting these sequences represents a viable strategy for identifying candidate molecules that could interfere with amyloid formation and toxicity of the parent proteins. However, the highly amyloidogenic and insoluble nature of these sequences has hampered efforts to develop high-throughput fibrillization assays.

Switch-peptides as folding precursors in self-assembling peptides and amyloid fibrillogenesis.

The study of conformational transitions of peptides has obtained considerable attention recently because of their importance as a molecular key event in a variety of degenerative diseases. However, the study of peptide self-assembly into beta-sheets and amyloid beta (Abeta) fibrils is strongly hampered by their difficult synthetic access and low solubility. We have recently developed a new concept termed switch-peptides that allows the controlled onset of polypeptide folding and misfolding at physiologic conditions.