Jonathan M Ellman

US Patent:

6344330, Feb 5, 2002

Filed:

Mar 27, 1998

Appl. No.:

09/049754

Inventors:

Jonathan A. Ellman - Oakland CA
Ingrid Choong - Berkeley CA

Assignee:

The Regents of the University of California - Oakland CA

International Classification:

A61K 31335

US Classification:

435 71, 549283, 549284, 549285, 549286, 549287, 549288, 549289, 549290, 435 6, 435 72, 436501, 436518, 424 111, 424 91, 4241781, 424 191, 530345, 5303891, 530402, 530807, 514449, 514450, 514451, 514452, 514453, 514454, 514455, 514456, 514457, 514458

Abstract:

The present invention is directed to novel methods for identifying small molecule ligands that are capable of binding with high affinity to a biological target molecule of interest. High affinity binding ligands identified by the described methods find use, for example, as small molecule lead compounds that may they themselves be, or may give rise to, novel therapeutic drugs. More specifically, the subject invention is directed to methods for identifying a ligand that binds to a target biological molecule of interest, wherein a population of small organic compounds are selected and then âpre-screenedâ to identify those that are capable of binding to the molecular target. The small organic compounds that are identified during the pre-screening as being capable of binding to the target (or structurally related analogs thereof) are then coupled in various combinations with a linker element to provide a library of potential ligands for binding to the target molecule that is then screened to identify ligands having very high binding affinities for the molecular target. Ligands obtained by this method and methods for using those ligands for inhibiting the interaction between two biological molecules are also provided.

US Patent:

6344334, Feb 5, 2002

Filed:

Mar 26, 1999

Appl. No.:

09/277461

Inventors:

Jonathan A. Ellman - Oakland CA
Ingrid Choong - Berkeley CA

Assignee:

The Regents of the University of California - Oakland CA

International Classification:

G01N 3353

US Classification:

435 71, 435 6, 435 72, 436501, 436518, 424 111, 424 91, 4241781, 4241931, 530345, 5303891, 530402, 530807, 514449, 514450, 514451, 514452, 514453, 514454, 514455, 514456, 514457, 514458, 549283, 549284, 549285, 549286, 549287, 549288, 549289, 549290

Abstract:

Method for identifying a drug lead compound that inhibits binding of target bioogical molecules (TBM) by contacting TBM with members of a library of candidate cross-linked target binding fragments (CXBF), each CXBF having at least two candidate target bindig fragments (CTBF), which are inhibitors of binding, linked to a cross-linker, and selecting CXBF that inhibit the binding of the TBM to a greater extent than either of the individual CTBF linked to said cross-linker, wherein the library of CXBF is produced by: (a) screening a population of CTBF capable of being chemically cross-linked by a cross-linker to identify a subpopulation of the CTBF that inhibit binding of the TBM; and (b) chemically cross-linking members of the subpopulation of CTBF or structurally related analogs thereof with a cross-linker to provide a library of CXBF, wherein at least one linking group comprises an oxime ether linking group.

US Patent:

6680178, Jan 20, 2004

Filed:

May 25, 2001

Appl. No.:

09/866132

Inventors:

Jennifer L. Harris - San Diego CA
Bradley J. Backes - San Diego CA
Jonathan A. Ellman - Oakland CA
Charles S. Craik - San Francisco CA

Assignee:

The Regents of the University of California - Oakland CA

International Classification:

C12Q 137

US Classification:

435 23, 435 24, 435 34, 435 4, 530324, 530350, 530334, 530345, 525 50, 525 541, 549288, 702 22, 702 30

Abstract:

A method is presented for the preparation and use of fluorogenic peptide substrates that allows for the configuration of general substrate libraries to rapidly identify the primary and extended specificity of enzymes, such as proteases. The substrates contain a fluorogenic-leaving group, such as 7-amino-4-carbamoylmethyl-coumarin (ACC). Substrates incorporating the ACC leaving group show comparable kinetic profiles as those with the traditionally used 7-amino-4-methyl-coumarin (AMC) leaving group. The bifunctional nature of ACC allows for the efficient production of single substrates and substrate libraries using solid-phase synthesis techniques. The approximately 3-fold increased quantum yield of ACC over AMC permits reduction in enzyme and substrate concentrations. As a consequence, a greater number of substrates can be tolerated in a single assay, thus enabling an increase in the diversity space of the library. Soluble positional protease substrate libraries of 137,180 and 6,859 members, possessing amino acid diversity at the P4-P3-P2-P1 and P4-P3-P2 positions, respectively, were constructed.

US Patent:

7001727, Feb 21, 2006

Filed:

Sep 26, 2003

Appl. No.:

10/670607

Inventors:

Jonathan A. Ellman - Oakland CA, US
Ingrid Choong - Berkeley CA, US

Assignee:

The Regents of the University of California - Oakland CA

International Classification:

C12Q 1/68

US Classification:

435 6, 435 4, 435 71

Abstract:

A library of candidate target binding fragments (CTBF's) each CTBF being a small organic molecule and having a linkable functional group (LFG) or blocked form thereof (BLFG), wherein the LFG or BLFG contains a linking group (LG), the LG being a disulfide group.

US Patent:

7119105, Oct 10, 2006

Filed:

Feb 5, 2004

Appl. No.:

10/774262

Inventors:

Jonathan A. Ellman - Oakland CA, US
Gary Lynch - Irvine CA, US
Irwin D. Kuntz - Greenbrae CA, US
Xiaoning Bi - Irvine CA, US
Christina E. Lee - San Francisco CA, US
A. Geoffrey Skillman - San Francisco CA, US
Tasir Haque - Wilmington DE, US

Assignee:

The Regents of the University of California - Oakland CA

International Classification:

A99Z 99/00

US Classification:

514321, 514323, 514330, 514375, 514414, 514417, 514616

Abstract:

The present invention relates to () non-peptide aspartyl protease inhibitors; (ii) methods for modulating the processing of an amyloid precursor protein (APP); (iii) methods for modulating the processing of a tau protein (τ-protein); and (iv) methods for treating neurodegenerative diseases. For instance, in one embodiment, the present invention provides a method for modulating the processing of an amyloid precursor protein (APP), the method comprising contacting a composition containing the APP with an aspartyl protease inhibitor having the formula:RRand Rare members independently selected from the group consisting of alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, aryloxyalkyl, substituted aryloxyalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heterocycles, substituted heterocycles, heterocyclicalkyl and substituted heterocyclicalkyl; and Rand Rare independently selected from the group consisting of hydrogen, halogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, aryloxyalkyl and substituted aryloxyalkyl; or Rand Rand the carbons to which they are bound join to form an optionally substituted carbocyclic or heterocyclic fused ring system having a total of 9- or 10-ring atoms within the fused ring system.

US Patent:

7629437, Dec 8, 2009

Filed:

Oct 15, 2003

Appl. No.:

10/686884

Inventors:

Jennifer L. Harris - San Diego CA, US
Bradley J. Backes - San Diego CA, US
Jonathan A. Ellman - Oakland CA, US
Charles S. Craik - San Francisco CA, US

Assignee:

The Regents of the University of California - Oakland CA

International Classification:

C12Q 1/00
C12Q 1/37
C07K 5/00
C07K 7/00

US Classification:

530300, 530324, 530334, 530345, 530350, 435 4, 435 23, 435 24, 435 34, 525 50, 525 541, 549288

Abstract:

A method is presented for the preparation and use of fluorogenic peptide substrates that allows for the configuration of general substrate libraries to rapidly identify the primary and extended specificity of enzymes, such as proteases. The substrates contain a fluorogenic-leaving group, such as 7-amino-4-carbamoylmethyl-coumarin (ACC). Substrates incorporating the ACC leaving group show comparable kinetic profiles as those with the traditionally used 7-amino-4-methyl-coumarin (AMC) leaving group. The bifunctional nature of ACC allows for the efficient production of single substrates and substrate libraries using solid-phase synthesis techniques.

US Patent:

8273926, Sep 25, 2012

Filed:

Jul 27, 2009

Appl. No.:

12/509985

Inventors:

Robert G. Bergman - Kensington CA, US
Jonathan A. Ellman - Oakland CA, US
Elena Arceo Rebollo - Oakland CA, US
Peter C. Marsden - Berkeley CA, US

Assignee:

The Regents of the University of California - Oakland CA

International Classification:

C07C 1/00
C07C 33/03

US Classification:

5689095, 585638, 585639

Abstract:

A method of preparing an olefin comprising: reacting a polyol in the presence of a carboxylic acid, such that an olefin is produced by the deoxygenation of the polyol. The reacting step can comprise (a) providing a composition comprising the polyol, (b) heating the composition, and (c) introducing the carboxylic acid to the composition wherein the introducing step occurs prior to, at the same time as, or subsequent to the heating step. In one embodiment, the polyol is glycerol, the carboxylic acid is formic acid, and the olefin is allyl alcohol, which is produced at a yield of about 80% or greater.

US Patent:

8361932, Jan 29, 2013

Filed:

May 2, 2007

Appl. No.:

12/299284

Inventors:

Gang L. Liu - Berkeley CA, US
Jonathan A. Ellman - Oakland CA, US
Luke P. Lee - Orinda CA, US
Fanqing Frank Chen - Moraga CA, US

Assignee:

The Regents of the University of California - Oakland CA

International Classification:

C40B 30/04
C40B 40/10
G01N 33/573

US Classification:

506 9, 435 74, 506 18

Abstract:

This invention pertains to the in vitro detection of proteases using a single peptide-conjugate nanocrescent surface enhanced Raman scattering (SERS) probes with at least nanomolar sensitivity. The probe enables detection of proteolytic activity in extremely small volume and at low concentration. In certain embodiments the probes comprise an indicator for the detection of an active protease, where the indicator comprises a nanocrescent attached to a peptide, where said peptide comprises a recognition site for the protease and a Raman tag attached to the peptide.