Design of non-aggregating variants of Aβ peptide.

Self association of the amyloid-β (Aβ42) peptide into oligomers, high molecular weight forms, fibrils and ultimately neuritic plaques, has been correlated with progressive cognitive decline in Alzheimer's disease. Thus, insights into the drivers of the aggregation pathway have the capacity to significantly contribute to our understanding of disease mechanism. Functional assays and a three-dimensional crystal structure of the P3 amyloidogenic region 18-41 of Aβ were used to identify residues important in self-association and to design novel non-aggregating variants of the peptide.

Central amyloid-β-specific single chain variable fragment ameliorates Aβ aggregation and neurotoxicity.

Anti-amyloid-β immunotherapies are a promising therapeutic approach for the treatment and prevention of Alzheimer's disease (AD). Single chain antibody fragments (scFv) are an attractive alternative to whole antibodies due to their small size, single polypeptide format and inability to stimulate potentially undesirable Fc-mediated immune effector functions. We have generated the scFv derivative of anti-Aβ monoclonal antibody, 1E8, known to target residues 17-22 of Aβ.

Ammonium hydroxide treatment of Aβ produces an aggregate free solution suitable for biophysical and cell culture characterization.

Alzheimer's disease is the leading cause of dementia in the elderly. Pathologically it is characterized by the presence of amyloid plaques and neuronal loss within the brain tissue of affected individuals. It is now widely hypothesised that fibrillar structures represent an inert structure.

Biodistribution of polymer hydrogel capsules for the delivery of therapeutics.

A key phase in the development of intelligently designed nanoparticle delivery vehicles for new therapeutic agents is to gain an understanding of their interaction with tissues and cells. We report a series of in vitro and in vivo experiments aimed at tracking a potential delivery vehicle for therapeutic agents, including vaccine peptides and drugs derived from poly(methacrylic acid) hydrogel capsules in certain organs and cell types. For the in vitro studies, two immortal liver-derived cell lines (Huh7 and Hepa1-6) and primary cultures of mouse hepatocytes were incubated with Alexa 647 labelled fluorescent capsules to track their internalization and intracellular distribution by confocal microscopy.

Engineered bacterially expressed polypeptides: assembly into polymer particles with tailored degradation profiles.

In nature, the sequence of amino acids in a protein is determined by the genetic code. Biosynthesis of polypeptides by bacteria can be used to exploit this natural process to afford exact control over properties such as molecular weight, chemical functionality, and structure. It is demonstrated how control over the positioning of functional groups can be used to tune the degradation of assembled polypeptide particles (see scheme).