Protagonist Therapeutics, Inc.

The University of Queensland

Mark Leslie Smythe

Gregory Thomas Bourne

Brian Troy Frederick

Jacob Ulrik Fog

Anne Pernille Tofteng Shelton

Simone Vink

Praveen Madala

Ashok Bhandari

David Y Liu

Jie Zhang

Roopa Taranath

Adam Stephenson

Wim Denis Frans Meutermans

Jack Urquhart Flanagan

Ross Peter McGeary

Peter Andrews

Michael John Dooley

Tran Trung Tran

Darryn Bryant

Stephen Long

Peter Adams

Peter Ronald Andrews

Brian T Frederick

The present invention relates, inter alia, to certain hepcidin peptide analogues, including peptides and dimers thereof, and to the use of the peptides and peptide dimers in the treatment and/or prevention of a variety of diseases, conditions or disorders, including treatment and/or prevention of iron overload diseases, which include hereditary hemochromatosis and iron-loading anemias, and other conditions and disorders described herein.

Hepcidin analogues and uses thereof

The present invention provides hepcidin analogues with improved in vivo half lives, and related pharmaceutical compositions and methods of use thereof.

Conjugated hepcidin mimetics

Analogues of hepcidin mimetics with improved in vivo half lives

The present invention relates, inter alia, to certain hepcidin peptide analogs, including peptides and dimers thereof, and to the use of the peptides and peptide dimers in the treatment and/or prevention of a variety of diseases, conditions or disorders, including treatment and/or prevention of iron overload diseases, which include hereditary hemochromatosis and iron-loading anemias, and other conditions and disorders described herein.

The present invention generally relates to compounds that inhibit haematopoietic-prostaglandin Dsynthase (H-PGDS), to compositions containing them and to their use in treating or preventing conditions and diseases associated with H-PGDS, such as allergies and inflammation.

Haematopoietic-prostaglandin D2 synthase inhibitors

A method of determining common three-dimensional structural features of protein surfaces is provided, as is use of representations of these common structures in molecular database searching and in designing focused molecular libraries. The method is particularly concerned with the analysis and representation of protein surfaces such as b-turns, loops and contact surfaces. In one form, the method identifies common locations and orientations of amino acid side-chains, simplified as C&#x3b1;-C&#x3b2; vectors. In another form, the method identifies common regions of surface charge represented by grid points in three-dimensional space. Further provided are common three dimensional structural features of proteins that can be used to search molecular databases for the purposes of identifying molecules that match these common three dimensional structural features. The common three dimensional structural features can also be used to focus de novo molecular generation to produce libraries containing molecules that have these common three dimensional structural features. Libraries of these structurally-related molecules may then be produced for the purposes of drug discovery.

Common protein surface shapes and uses therefor

This invention relates to methods for preparing cyclic peptides and peptidomimetic compounds in solution and bound to solid supports, and to cyclic peptide or peptidomimetic libraries for use in drug screening programmes. In particular, the invention relates to a generic strategy for synthesis of cyclic peptides or peptidomimetics that enables the efficient synthesis under mild conditions of a wide variety of desired compounds. Two approaches were evaluated for their improvements in solution and solid phase synthesis of small cyclic peptides: positioning reversible N-amide substituents in the sequence; and applying native ligation chemistry in an intramolecular sense. Systematic investigation of the effects of preorganizing peptides prior to cyclisation by using peptide cyclisation auxiliaries, and developing new linkers and peptide cyclisation auxiliaries to aid cyclic peptide synthesis gives surprising improvements in both yields and purity of products compared to the prior art methods. The combination of these technologies provides a powerful generic approach for the solution and solid phase synthesis of small cyclic peptides. The ring contraction and N-amide substitution technology of the invention provide improved methods for the synthesis of cyclic peptides and peptidomimetics. When used in conjunction with linker strategies, this combination provides solid-phase avenues to cyclic peptides and peptidomimetics.

Auxiliary for amide bond formation

This invention relates to methods for preparing cyclic peptides and peptidomimetic compounds in solution and bound to solid supports, and to cyclic peptide or peptidomimetic libraries for use in drug screening programs. In particular, the invention relates to a generic strategy for synthesis of cyclic peptides or peptidomimetics that enables the efficient synthesis under mild conditions of a wide variety of desired compounds. Two approaches were evaluated for their improvements in solution and solid phase synthesis of small cyclic peptides: positioning reversible N-amide substituents in the sequence; and applying native ligation chemistry in an intramolecular sense. Systematic investigation of the effects of preorganising peptides prior to cyclisation by using peptide cyclisation auxiliaries, and developing new linkers and peptide cyclisation auxiliaries to aid cyclic peptide synthesis gives surprising improvements in both yields and purity of products compared to the prior art methods. The combination of these technologies provides a powerful generic approach for the solution and solid phase synthesis of small cyclic peptides. The ring contraction and N-amide substitution technology of the invention provide improved methods for the synthesis of cyclic peptides and peptidomimetics. When used in conjunction with linker strategies, this combination provides solid-phase avenues to cyclic peptides and peptidomimetics.

Synthesis of cyclic peptides

A method of protein engineering is provided wherein a searchable computer database is created comprising entries in the form of descriptions of a location and orientation in 3D space of side chains of the constituent amino acid residues of a framework protein. A query is created which corresponds to a description of a location and orientation in 3D space of respective side chains of amino acid residues of a sample protein. The location and orientation in 3D space of constituent side-chains is preferably described as a C&#x3b1;&#x2013;C&#x3b2; vector. The query is used to search the database and thereby identify a hit which corresponds to a framework protein having structural similarity with said sample protein. Framework protein 'hits' so identified may be suitable candidates for further modification. A particular advantage of the present invention is that a modified framework protein may display one or more desired characteristics, such as a function similar to or inhibitory of the sample protein.

Protein engineering

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Bardon, Australia

Mark Leslie Smythe