Gryphon Therapeutics, Inc.

Amylin Pharmaceuticals, Inc.

James A Bradburne

Stephen B H Kent

Paolo Botti

Christie L Hunter

Gerd G Kochendoerfer

Shiah-yun Chen

Sonya Cressman

Donald W Low

Jill G Wilken

Gerd Kochendoerfer

The present invention relates to methods and compositions for modifying peptides, polypeptides and proteins with polymers, especially glyco-mimetic polymers, so as to improve their biological activity or pharmacokinetic properties. The invention further provides methods and uses for such polymer-modified peptides, polypeptides and proteins. The invention is particularly suitable for use in the synthesis of polymer-modified synthetic bioactive proteins (FIG.D), and of pharmaceutical compositions that contain such proteins.

Polymer-modified synthetic proteins

The present invention concerns methods and compositions for extending the technique of native chemical ligation of a wider range of peptides, polypeptides, other polymers and other molecules via an amide bond (see FIG.). The invention further provides methods and uses for such proteins and derivatized proteins. The invention is particularly suitable for use in the synthesis of optionally polymer-modified, synthetic bioactive proteins, and of pharmaceutical compositions that contain such proteins.

Pseudo native chemical ligation

The invention is directed to nucleophile-stable thioester generating compounds comprising a carboxyester thiol. The compounds have wide applicability in organic synthesis, including the generation of peptide-, polypeptide- and other polymer-thioesters. The invention is particularly useful for generating activated-thioesters from precursors that are made under conditions in which strong nucleophiles are employed, such as peptides or polypeptides made using Fmoc SPPS, as well as multi-step ligation or conjugation schemes that require (or benefit from the use of) compatible selective approaches for directing a specific ligation or conjugation reaction of interest.

Nucleophile-stable thioester generating compounds, methods of production and use

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Redwood City, CA, United States of America

James A Bradburne