Amyloid -Protein Aggregation Inhibitors

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N EW TECHNOLOGY DISCLOSURE Amyloid -Protein Aggregation Inhibitors Novel disubstituted peptides disrupt the formation of the amyloid -protein fibrils associated with Alzheimer’s disease, and destabilize already-formed fibrils. Patent Status: Patented Technology Status: Animal studies in progress Terms: Exclusive or Non-Excl. Availability: Immediate Inhibition of amyloid -protein aggregation and dissolution of existing aggregates may provide an effective treatment for Alzheimer’s disease. Principal Investigator Robert P. Hammer Long-standing evidence shows that cerebral deposition of amyloid -protein (A ) fibrils and plaque plays a central role in the progressive neural degeneration of Alzheimer’s William A. Pryor Professor disease. There is therefore great interest in controlling the proteolytic conversion of Dept. of Chemistry amyloid precursor protein (APP) to A , or modulating the Applications [email protected] seemingly irreversible aggregation of A into -pleated sheets that form the damaging fibrils and plaque. Potential treatment for We have developed several amyloid aggregation- Alzheimer’s disease mitigating peptide (AAMP) analogs that display signifi- Potential for other LSU OIP 0212 cantly better in vitro and in vivo interference of A fibril- proteopathies: logenesis than previously existing peptide analogs, and Prion diseases For licensing, contact: that can dissolve already-formed fibrils in vitro. Parkinson’s disease Amyotrophic lateral sclerosis Peter J. Kelleher Our fibril inhibitors are designed to interact with A via Associate Vice-Chancellor hydrogen bonding and side-chain interactions at the fi- Nanotechnology bril’s -pleated sheet edge, preventing further A aggre- Modulation of peptide-based Office of Intellectual Property, gation by blocking the hydrogen bonding that appears to structures Commercialization and Development stabilize fibril formation. We have shown that while pure 206 Louisiana Emerging Technology Center A solutions form fibrils in vitro, our AAMP/A mix- Baton Rouge, LA 70803 tures show no fibrillization or gelation even after months at room temperature. Preliminary animal studies are consistent Phone: 225-615-8967 with these in vitro results. Fax: 225-615-8965 E-mail: [email protected] Our AAMPS are very stable and do not aggregate in solu- RESEARCH & ECONOMIC tion. DEVELOPMENT Non-Confidential Disclosure. © Louisiana State University 2007. All Rights Reserved. .

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Analysis of Different Evolutionary Strategies to Prevent Protein Aggregation
Universitat Autònoma de Barcelona Departament de Bioquímica i Biologia Molecular and Institut de Biotecnologia i Biomedicina Analysis of Different Evolutionary Strategies to Prevent Protein Aggregation Ricardo Graña Montes Bellaterra, December 2014 Universitat Autònoma de Barcelona Departament de Bioquímica i Biologia Molecular and Institut de Biotecnologia i Biomedicina Analysis of Different Evolutionary Strategies to Prevent Protein Aggregation Doctoral thesis submitted by Ricardo Graña Montes in candidacy for the degree of Ph.D. in Biochemistry, Molecular Biology and Biomedicine from the Universitat Autònoma de Barcelona. The work described herein has been performed at the Department de Bioquímica i Biologia Molecular and at the Institut de Biotecnologia i Biomedicina, under the supervision of Prof. Salvador Ventura Zamora. Ricardo Graña Montes Prof. Salvador Ventura Zamora Bellaterra, December 2014 SUMMARY IN ENGLISH In the last 15 years, the study of protein aggregation has evolved from a mostly neglected topic of protein chemistry to a highly dynamic research area which has expanded its implications through different fields including biochemistry, biotechnology, nanotechnology and biomedicine. The analysis of protein aggregation has attracted a particular interest in the biomedical and biotechnological areas. Because, on one side, the formation of insoluble protein deposits is associated to an increasing number of human disorders, many of which present fatal pathological consequences. And on the other hand, aggregation is a frequent shortcoming in the recombinant expression of proteins at the industrial level, such as in the production of proteinaceous therapeutic agents like antibodies. Consequently, the survey of mechanisms to prevent protein aggregation is currently the focus of deep investigation with the aim to develop preventive or therapeutic methods for the intervention of these depositional disorders and to enhance the yield in the biotechnological production of proteins.
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