Stephen P Kent

US Patent:

20020132975, Sep 19, 2002

Filed:

Nov 15, 2001

Appl. No.:

09/987655

Inventors:

Lynne Canne - Pacifica CA, US
Stephen Kent - San Francisco CA, US
Reyna Simon - Los Gatos CA, US

Assignee:

Gryphon Sciences

International Classification:

C07K016/00

US Classification:

530/324000

Abstract:

The present invention provides methods, apparatus and kits for synthesizing assembled peptides and proteins on a solid phase with sequential ligation of three or more unprotected peptide segments using chemoselective and mild ligation chemistries in aqueous solution. Also provided are methods of monitoring solid phase sequential ligation reactions using MALDI or electrospray ionization mass spectrometry of reaction products.

US Patent:

20020169282, Nov 14, 2002

Filed:

Nov 15, 2001

Appl. No.:

09/987675

Inventors:

Lynne Canne - Pacifica CA, US
Stephen Kent - San Francisco CA, US
Reyna Simon - Los Gatos CA, US

Assignee:

Gryphon Sciences

International Classification:

C07K001/04

US Classification:

530/334000

Abstract:

The present invention provides methods, apparatus and kits for synthesizing assembled peptides and proteins on a solid phase with sequential ligation of three or more unprotected peptide segments using chemoselective and mild ligation chemistries in aqueous solution. Also provided are methods of monitoring solid phase sequential ligation reactions using MALDI or electrospray ionization mass spectrometry of reaction products.

US Patent:

20030018169, Jan 23, 2003

Filed:

Jul 30, 2002

Appl. No.:

10/207330

Inventors:

Gerd Kochendoerfer - Oakland CA, US
Christie Hunter - San Francisco CA, US
Stephen Kent - San Francisco CA, US
Paolo Botti - San Francisco CA, US

International Classification:

C07K014/705

US Classification:

530/350000, 530/408000, 530/409000

Abstract:

The present invention relates to methods and compositions for lipid matrix-assisted chemical ligation and synthesis of membrane polypeptides that are incorporated in a lipid matrix. The invention is exemplified in production of a prefolded membrane polypeptide embedded within a lipid matrix via stepwise chemoselective chemical ligation of unprotected peptide segments, where at least one peptide segment is embedded in a lipid matrix. Any chemoselective reaction chemistry amenable for ligation of unprotected peptide segments can be employed. Suitable lipid matrices include liposomes, micelles, cell membrane patches and optically isotropic cubic lipidic phase matrices. Prefolded synthetic and semi-synthetic membrane polypeptides synthesized according to the methods and compositions of the invention also permit site-specific incorporation of one or more detectable moieties, such as a chromophore, which can be conveniently introduced during synthesis. The methods and compositions of the invention have multiple uses. For example, they can be used to assay ligand binding to membrane polypeptides and domains comprising a receptor, and thus are extremely useful for structure/function studies, drug screening/selection/design, and diagnostics and the like, including high-throughput applications. The methods and compositions of the invention are particularly suited for FRET analyses of previously inaccessible membrane polypeptides.

US Patent:

20030149234, Aug 7, 2003

Filed:

Jan 9, 2003

Appl. No.:

10/332454

Inventors:

Paolo Botti - Piacenza, IT
James Bradburne - Redwood City CA, US
Stephen Kent - San Francisco CA, US

International Classification:

C07K007/00
C07C327/02

US Classification:

530/300000, 558/250000

Abstract:

The invention is directed to nucleophile-stable thioester generating compounds comprising an orthothioloester or a carboxyester thiol, methods of production and use. The compounds and methods 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.

US Patent:

20030191291, Oct 9, 2003

Filed:

Jan 13, 2003

Appl. No.:

10/332696

Inventors:

Gerd Kochendoerfer - Oakland CA, US
Paolo Botti - Piacenza, IT
James Bradburne - Redwood City CA, US
Sonya Cressman - Ladysmith, CA
Christine Hunter - San Mateo CA, US
Stephen Kent - San Francisco CA, US
Donald Low - Burlingame CA, US

International Classification:

C07K014/575

US Classification:

530/397000

Abstract:

Synthetic erythropoiesis stimulating proteins are provided. Also provided are methods for synthesizing the proteins. The invention further relates to derivatives of such synthetic erythropoiesis stimulating proteins that are polymer-modified in a defined manner. Methods and uses for such proteins and derivatized proteins are also provided.

US Patent:

20030208046, Nov 6, 2003

Filed:

Jan 8, 2003

Appl. No.:

10/332386

Inventors:

Christie Hunter - San Mateo CA, US
Paolo Botti - Piacenza, IT
James Bradburne - Redwood City CA, US
Sonya Cressman - Ladysmith, CA
Stephen Kent - San Francisco CA, US
Gerd Kochendoerfer - Oakland CA, US
Donald Low - Burlingame CA, US

International Classification:

A61K038/19
C07K014/53

US Classification:

530/351000, 424/085100, 514/012000

Abstract:

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.

US Patent:

20040115774, Jun 17, 2004

Filed:

Jan 8, 2003

Appl. No.:

10/332385

Inventors:

Gerd Kochendoerfer - Oakland CA, US
Paolo Botti - Piacenza, IT
James Bradburne - Redwood City CA, US
Sonya Cressman - Ladysmith BC, US
Christie Hunter - San Mateo CA, US
Stephen Kent - San Francisco CA, US
Donald Low - Burlingame CA, US
Jill Wilken - Walnut Creek CA, US

International Classification:

C07K014/54
C07H021/04
C12P021/02

US Classification:

435/069500, 435/320100, 435/325000, 530/351000, 536/023500

Abstract:

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.

US Patent:

20040138412, Jul 15, 2004

Filed:

Jan 15, 2003

Appl. No.:

10/333017

Inventors:

Paolo Botti - Piacenza, IT
James Bradburne - Redwood City CA, US
Stephen Kent - San Francisco CA, US
Donald Low - Burlingame CA, US

International Classification:

C12P019/34
C07K007/08

US Classification:

530/324000, 530/409000

Abstract:

The invention is directed to methods and compositions for chemical ligation of components comprising a first component having a carboxythioester, and preferable an -carboxythioester, moiety and a second component having an N-substituted, and preferably an N-substituted, 2 or 3 carbon chain alkyl or aryl thiol to give a ligation product having an N-substituted amide bond at the ligation site. The reactants of the invention are chemoselective, and the alkyl or aryl thiol moiety is removable from the ligation product. Removal of the alkyl or aryl thiol gives a native amide bond at the ligation site. The methods and compositions of the invention are particularly useful for ligation of peptides and polypeptides. The ligation system of the invention is applicable to a wide variety of molecules, and thus can be exploited to generate peptides, polypeptides and other amino acid containing polymers having a native amide bond at the ligation site.