University of Toronto

Reflexion Pharmaceuticals, Inc.

Maruti Uppalapati

Dana Ault-Riche

Sachdev Singh Sidhu

Stephen B H Kent

Aaron Kerman

Scaffolded peptidic libraries and methods of screening the same for specific binding to a target protein are provided. Each library includes distinct peptidic compounds that include a scaffold domain and a distinct variable domain. A variety of libraries are provided where each library is based on an underlying peptidic scaffold having a structural motif. In some embodiments, the peptidic scaffold is a small protein having a protein-protein interaction surface. Libraries of polynucleotides that encode a variety of peptidic compounds are provided. These libraries find use in a variety of applications in which specific binding to target molecules, e.g., target proteins is desired. Also provided are methods of making the libraries and methods of screening the libraries for binding to a target.

Scaffolded peptidic libraries and methods of making and screening the same

GB1 peptidic compounds that specifically bind to a hemagglutinin target protein, and libraries that include the same, as well as methods of making and using the same, are provided. Also provided are methods and compositions for making and using the compounds. Also provided are hemagglutinin mimics and fragments and methods of using the same, including methods of screening for GB1 peptidic compounds and methods of using conjugates the mimics as influenza A vaccines. Aspects of the invention include methods of screening libraries of L-peptidic compounds for specific binding to a D-peptidic hemagglutinin target protein. Once a L-peptidic compound has been identified that specifically binds to the D-peptidic hemagglutinin target protein, the D-enantiomer of the selected L-peptidic compound may be produced. In some embodiments, the D-enantiomer of the selected L-peptidic compound binds to, and in some instances, neutralizes influenza virus particles.

Broad spectrum influenza A neutralizing vaccines and D-peptidic compounds, and methods for making and using the same

Methods and compositions for identifying D-peptidic compounds that specifically bind target proteins are provided. Aspects of the methods include screening libraries of 20 residue or more L-peptidic compounds for specific binding to 40 residue or more D-target proteins. Once a L-peptidic compound has been identified that specifically binds to the D-target protein, the D-enantiomer of that compound may be produced.

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Toronto, Canada

Maruti Uppalapati