Chiron Corporation

Scios Inc.

Eli Lilly and Company

Novartis Vaccines & Diagnostics, Gmbh

Koasn Biosciences Incorporated

Ziyang Zhong

Angelica Medina-Selby

Doris Guenzi Coit

Stephen David Harrison

John Andrew Hall

Maria Calderon-Cacia

Steve H Nguyen

Eric Y Fang

Barbara Cordell

Qiang Xu

Sheila P Little

Yu-Wang Liu

Diana Hom Quon

Paul Andrew Hyslop

Edward Marion Johnstone

Frauke Schimmöller

Steven Wyatt Queener

Tinggui Yin

Peter J Licari

Douglas I Buckley

Taymar E Hartman

Indu Isaacs

N Stephen Pollitt

John G Augustine

Peter A Stathis

Formulations of desoxyepothilones are stable before and after dilution into aqueous media.

Therapeutic formulations of desoxyepothilones

The invention provides truncated GSK3 polypeptides capable of crystallization, including GSK3&#x3b1; and GSK3&#x3b2; polypeptides, and use of these polypeptides to identify and optimize GSK3 inhibitors. Also provided are GSK3 polypeptides having at least one substituted amino acid that differs from wild-type GSK3, wherein the substituted amino acid is incapable of being phosphorylated. The invention finds use in providing methods of identifying and optimizing compounds useful for treating diseases mediated by GSK3 activity, including Alzheimer's disease, type 2 diabetes, and inflammation.

GSK3 polypeptides

The invention concerns a novel &#x3b2;-secretase, a method of partially purifying this novel &#x3b2;-secretase, and its use in assays to screen for potential drug candidates against Alzheimer's disease and other neurological diseases. The novel &#x3b2;-secretase has an estimated molecular weight of about 32-39 kDa or 22-26 kDa in HEK293 cell membrane extracts and human brain samples, respectively, as calculated from radiation inactivation analysis, and has a pH optimum at about pH 6.5-7.0.

&#x3b2;-secretase and modulation of &#x3b2;-secretase activity

The invention concerns a novel &#x3b2;-secretase, a method of partially purifying this novel &#x3b2;-secretase, and its use in assays to screen for potential drug candidates against Alzheimer's disease and other neurological diseases. The novel &#x3b2;-secretase has an estimated molecular weight of about 32&#x2013;39 kDa or 22&#x2013;26 kDa in HEK293 cell membrane extracts and human brain samples, respectively, as calculated from radiation inactivation analysis, and has a pH optimum at about pH 6.5&#x2013;7.0.

The invention provides truncated GSK3 polypeptides capable of crystallization, including GSK3&agr; and GSK3&bgr; polypeptides, and use of these polypeptides to identify and optimize GSK3 inhibitors. Also provided are GSK3 polypeptides having at least one substituted amino acid that differs from wild-type GSK3, wherein the substituted amino acid is incapable of being phosphorylated. The invention finds use in providing methods of identifying and optimizing compounds useful for treating diseases mediated by GSK3 activity, including Alzheimer's disease, type 2 diabetes, and inflammation.

A method is described for producing a peptide having a pI above 8 or below 5 wherein the peptide is expressed as a fusion protein in which it is linked to a fusion partner through an acid cleavage site. The peptide is released from the fusion partner by acid cleavage in the absence of chaotrope. The fusion partner and its acid cleavage products, if any, have a net charge sufficiently different from that of the desired peptide to allow isolation of the peptide by ion-exchange chromatography.

Method for producing a peptide with a pI above 8 or below 5

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Ziyang Zhong