Web Desc
Proteolytic Enzymes as Therapeutic Targets
Organizer(s): Robert L. Heinrikson and Jan Potempa
Date: February 03 - 08, 2002
Location: Keystone Resort, Keystone, CO, USA
Sponsored in part by The Director's Sponsor Fund
Summary of Meeting:
Proteolytic enzymes play roles in almost every biological system, and they have proven to be important therapeutic targets for drug development. Inhibitors of angiotensin converting enzyme (ACE) represent a major success in benefiting sufferers of hypertension. HIV-protease inhibitors have literally changed the duration and quality of life of AIDS patients. Discoveries of new proteases continue unabated, and it remains a problem of how to develop inhibitors of these enzymes as drugs. Currently, the proteases involved in liberating the toxic Abeta peptide that accumulates in Alzheimer's Disease represent a topic of intense interest. Cysteinyl proteases such as caspases and virally encoded enzymes are also current targets with inhibitors entering clinical trials. This meeting will update, and facilitate scientific exchanges among investigators working on a spectrum of proteases that have been shown to participate in biological pathways relevant to human disease.
Discounted Abstract Deadline: November 2 2001
Discounted Registration Deadline: December 3 2001
We gratefully acknowledge the generous grant for this conference provided by:

National Institute on Aging (NIA)
Grant No. 1 R13 AG20281-01
We appreciate the organizations that provide Keystone Symposia with additional support, such as marketing and advertising:

Click here to view more of these organizations
Special thanks to the following for their support of Keystone Symposia initiatives to increase participation at this meeting by scientists from underrepresented backgrounds:

Click here to view more of these organizations

Program

Sunday, February 03 | 4:00PM - 7:00PM
Registration
Room: Quandary Foyer


Sunday, February 03 | 6:15PM - 7:15PM
Welcome
Room: Quandary Foyer


Sunday, February 03 | 7:15PM - 7:30PM
Orientation
Room: Quandary


Sunday, February 03 | 7:30PM - 8:30PM
Keynote Address
Room: Quandary

Speaker 1 of 1
Charles T. Esmon, Oklahoma Medical Research Foundation, USA
Regulation of Blood Clotting and Inflammation by the Protein C Anticoagulant Pathway

Monday, February 04 | 7:00AM - 8:00AM
Breakfast
Room: Castle Peak 3-4


Monday, February 04 | 8:00AM - 11:00AM
Protease Targets in Alzheimer's Disease: New Therapeutic Per
spectives

Room: Castle Peak 1-2

Speaker 3 of 3
Yong Shen, Sun Health Research Institute, USA
Short Talk: Alteration of beta-Secretase (BACE) Expression in Sporadic AD Brain

Monday, February 04 | 8:00AM - 11:00AM
Protease Targets in Alzheimer's Disease: New Therapeutic Per
spectives

Room: Castle Peak 1-2

Speaker 2 of 3
Sukanto Sinha, Elan Pharmaceuticals, Inc., USA
Bace/beta-Secretase Target: Biology and Inhibition

Monday, February 04 | 8:00AM - 11:00AM
Protease Targets in Alzheimer's Disease: New Therapeutic Per
spectives

Room: Castle Peak 1-2

Speaker 1 of 3
* Dennis J. Selkoe, Harvard Medical School, USA
Intramembranous Proteolysis of Notch and APP in the Genesis and Treatment of Alzheimer's Disease

Monday, February 04 | 9:20AM - 9:40AM
Coffee Break
Room: Castle Peak Foyer


Monday, February 04 | 11:00AM - 1:00PM
Poster Setup
Room: Castle Peak 3-4


Monday, February 04 | 1:00PM - 9:30PM
Poster Viewing
Room: Castle Peak 3-4


Monday, February 04 | 2:00PM - 4:00PM
Workshop 1: Aspartyl Proteinase and Approaches to AD Therapy
Room: Castle Peak 1-2

Speaker 4 of 4
Hyman Engelberg, Cedars Sinai Medical Center, USA
Heparin Inhibits Proteolytic Enzymes Involved in Alzheimer's Disease Pathogenesis

Monday, February 04 | 2:00PM - 4:00PM
Workshop 1: Aspartyl Proteinase and Approaches to AD Therapy
Room: Castle Peak 1-2

Speaker 3 of 4
Alex Loukas, George Washington University Medical Center, USA
Compatibility Between Hookworm Aspartyl Proteases and Host Hemoglobins is a Determinant of Host Range.

Monday, February 04 | 2:00PM - 4:00PM
Workshop 1: Aspartyl Proteinase and Approaches to AD Therapy
Room: Castle Peak 1-2

Speaker 2 of 4
Yong-Tae Kim, Oklahoma Medical Research Foundation, USA
Enzymic Properties of Recombinant BACE2

Monday, February 04 | 2:00PM - 4:00PM
Workshop 1: Aspartyl Proteinase and Approaches to AD Therapy
Room: Castle Peak 1-2

Speaker 1 of 4
* Dennis J. Selkoe, Harvard Medical School, USA

Monday, February 04 | 4:00PM - 4:30PM
Coffee & Snacks Available
Room: Castle Peak Foyer


Monday, February 04 | 4:30PM - 6:30PM
The Ups and Downs of Proteinase Inhibitor-Based Therapy of V
iral Infections

Room: Castle Peak 1-2

Speaker 4 of 4
Bret B. Beyer, University of Florida, USA
Short Talk: The Use of Chromogenic Libraries of Octapeptides to Elucidate Subsite Preference of Plasmodium Aspartic Proteinases

Monday, February 04 | 4:30PM - 6:30PM
The Ups and Downs of Proteinase Inhibitor-Based Therapy of V
iral Infections

Room: Castle Peak 1-2

Speaker 3 of 4
Cynthia F. Shuman, Uppsala University, Sweden
Short Talk: Studies of Drug Resistant Variants of HIV-1 Protease and Inhibitors Using Interaction Kinetic Analysis

Monday, February 04 | 4:30PM - 6:30PM
The Ups and Downs of Proteinase Inhibitor-Based Therapy of V
iral Infections

Room: Castle Peak 1-2

Speaker 2 of 4
Peter S. Dragovich, Pfizer Global Research & Development, USA
Orally Bioavailable Human Rhinovirus 3C Protease Inhibitors

Monday, February 04 | 4:30PM - 6:30PM
The Ups and Downs of Proteinase Inhibitor-Based Therapy of V
iral Infections

Room: Castle Peak 1-2

Speaker 1 of 4
* Ben M. Dunn, University of Florida College of Medicine, USA
Overview of Viral Peptidases as Therapeutic Targets

Monday, February 04 | 6:30PM - 8:30PM
Cash Bar
Room: Castle Peak 3-4


Monday, February 04 | 6:30PM - 7:30PM
Welcome Mixer
Room: Castle Peak 3-4


Monday, February 04 | 7:30PM - 9:30PM
Poster Session 1: Aspartyl , Cysteinyl and Serine Proteases
Room: Castle Peak 3-4


Tuesday, February 05 | 7:00AM - 8:00AM
Breakfast
Room: Castle Peak 3-4


Tuesday, February 05 | 8:00AM - 11:00AM
Caspases as Therapeutic Targets
Room: Castle Peak 1-2

Speaker 1 of 4
* Nancy A. Thornberry, Kallyope, Inc., USA
Proteoses and Their Roles in Apoptosis

Tuesday, February 05 | 8:00AM - 11:00AM
Caspases as Therapeutic Targets
Room: Castle Peak 1-2

Speaker 2 of 4
Guy S. Salvesen, Sanford-Burnham Medical Research Institute, USA
To Live or to Die: Regulation of Apoptosis Revealed at the Molecular Level

Tuesday, February 05 | 8:00AM - 11:00AM
Caspases as Therapeutic Targets
Room: Castle Peak 1-2

Speaker 3 of 4
Mark A. Murcko, Disruptive Biomedical, LLC, USA
Clinical Evaluation of an Inhibitor of Caspase 1

Tuesday, February 05 | 8:00AM - 11:00AM
Caspases as Therapeutic Targets
Room: Castle Peak 1-2

Speaker 4 of 4
Sandra Moore Waugh, University of California, San Francisco, USA
Short Talk: Structural Determinants of Specificity among Proteases with High Sequence Identity and Dramatically Different Substrate Specificities

Tuesday, February 05 | 9:20AM - 9:40AM
Coffee Break
Room: Castle Peak Foyer


Tuesday, February 05 | 11:00AM - 1:00PM
Poster Setup
Room: Castle Peak 3-4


Tuesday, February 05 | 1:00PM - 9:30PM
Poster Viewing
Room: Castle Peak 3-4


Tuesday, February 05 | 2:00PM - 4:00PM
Workshop 2: Cysteinyl, Serine and Metalloproteases
Room: Castle Peak 1-2

Speaker 1 of 6
* Robert L. Heinrikson, Pfizer Inc., USA

Tuesday, February 05 | 2:00PM - 4:00PM
Workshop 2: Cysteinyl, Serine and Metalloproteases
Room: Castle Peak 1-2

Speaker 2 of 6
Fabien Lecaille, Mount Sinai School of Medicine, USA
Identification of Cathepsin K Residues Necessary for Complex Formation with Glycosaminoglycans

Tuesday, February 05 | 2:00PM - 4:00PM
Workshop 2: Cysteinyl, Serine and Metalloproteases
Room: Castle Peak 1-2

Speaker 3 of 6
Nadine Hornig, Cancer Research UK, UK
Regulation of the Novel Cell Cycle Protease ‘Separase’ in Yeast

Tuesday, February 05 | 2:00PM - 4:00PM
Workshop 2: Cysteinyl, Serine and Metalloproteases
Room: Castle Peak 1-2

Speaker 4 of 6
Peter J. Tummino, Janssen Pharmaceutical Companies of Johnson and Johnson, USA
Hydrolysis of Biologically Active Peptides by Human Angiotensin-Converting Enzyme-Related Carboxypeptidase (ACE2)

Tuesday, February 05 | 2:00PM - 4:00PM
Workshop 2: Cysteinyl, Serine and Metalloproteases
Room: Castle Peak 1-2

Speaker 5 of 6
Wenyan Wang, Schering-Plough Research Institute, USA
The Conserved C-Terminal Threonine of Hepatitis C Virus NS3 Regulates Autoproteolysis and Ensures Proper Assembly of the NS3/NS4A Complex

Tuesday, February 05 | 2:00PM - 4:00PM
Workshop 2: Cysteinyl, Serine and Metalloproteases
Room: Castle Peak 1-2

Speaker 6 of 6
Martha A. O'Brien, Promega Corporation, USA
Development of Luminescent Protease Assays

Tuesday, February 05 | 4:00PM - 4:30PM
Coffee & Snacks Available
Room: Castle Peak Foyer


Tuesday, February 05 | 4:30PM - 6:30PM
Secreted Proteases in Cancer
Room: Castle Peak 1-2

Speaker 1 of 4
* Lynn M. Matrisian, Vanderbilt University School of Medicine, USA
Secreted Proteinases in Cancer: The Matrix Metalloproteinase Experience

Tuesday, February 05 | 4:30PM - 6:30PM
Secreted Proteases in Cancer
Room: Castle Peak 1-2

Speaker 2 of 4
Ralph Weissleder, Massachusetts General Hospital, USA
In vivo Imaging of Protease Activity

Tuesday, February 05 | 4:30PM - 6:30PM
Secreted Proteases in Cancer
Room: Castle Peak 1-2

Speaker 3 of 4
Bonnie F. Sloane, Wayne State University School of Medicine, USA
Cell Surface Proteolysis: Contribution of Cysteine Proteases

Tuesday, February 05 | 4:30PM - 6:30PM
Secreted Proteases in Cancer
Room: Castle Peak 1-2

Speaker 4 of 4
Rainer Friedrich, Friedrich Miescher Institute for Biomedical Research, Switzerland
Short Talk: Crystal Structure of the Catalytic Domain of MTSP-1, A Type-II Transmembrane Serine Proteinase Implicated in Cancer

Tuesday, February 05 | 6:30PM - 7:30PM
Welcome Mixer
Room: Castle Peak 3-4


Tuesday, February 05 | 6:30PM - 8:30PM
Cash Bar
Room: Castle Peak 3-4


Tuesday, February 05 | 7:30PM - 9:30PM
Poster Session 2: Metalloproteinases, Regulation and General
Topics
Room: Castle Peak 3-4


Wednesday, February 06 | 7:00AM - 8:00AM
Breakfast
Room: Castle Peak 3-4


Wednesday, February 06 | 8:00AM - 11:00AM
Exopeptidases
Room: Castle Peak 1-2

Speaker 1 of 5
* Brian W. Matthews, University of Oregon, USA
Structure and Function of E. coli Methionine Aminopeptidases

Wednesday, February 06 | 8:00AM - 11:00AM
Exopeptidases
Room: Castle Peak 1-2

Speaker 2 of 5
Hans-Ulrich Demuth, Probiodrug AG, Germany
DPIV Inhibitors in Diabetes Treatment

Wednesday, February 06 | 8:00AM - 11:00AM
Exopeptidases
Room: Castle Peak 1-2

Speaker 3 of 5
Francesc X. Aviles, Universidad Autonoma de Barcelona, Spain
Inhibitors of Metallocarboxypeptidases. Potential Antitumor and Fibrinolytic Agents

Wednesday, February 06 | 8:00AM - 11:00AM
Exopeptidases
Room: Castle Peak 1-2

Speaker 4 of 5
C. Robin Ganellin, University College London, UK
Design of Butabindide, The First Inhibitor of Tripeptidyl Peptidase II

Wednesday, February 06 | 8:00AM - 11:00AM
Exopeptidases
Room: Castle Peak 1-2

Speaker 5 of 5
Jan Konvalinka, Institute of Organic Chemistry and Biochemistry, Czech Republic
Short Talk: Structure and Activity of Recombinant Human Glutamate Carboxypeptidase II

Wednesday, February 06 | 9:20AM - 9:40AM
Coffee Break
Room: Castle Peak Foyer


Wednesday, February 06 | 4:00PM - 4:30PM
Coffee & Snacks Available
Room: Castle Peak Foyer


Wednesday, February 06 | 4:30PM - 7:00PM
Targeting Bacterial and Parasitic Proteinases
Room: Castle Peak 1-2

Speaker 1 of 5
* Jan Potempa, University of Georgia, USA
Proteolytic Enzymes of Pathogenic Bacteria as Virulence Factors and Potential Targets for Drug Development

Wednesday, February 06 | 4:30PM - 7:00PM
Targeting Bacterial and Parasitic Proteinases
Room: Castle Peak 1-2

Speaker 2 of 5
Michael A. Curtis, University of London, UK
Proteinases of Porphyromonas gingivalis as Targets for Proteinase Inhibitor-Based Treatment of Periodontal Disease

Wednesday, February 06 | 4:30PM - 7:00PM
Targeting Bacterial and Parasitic Proteinases
Room: Castle Peak 1-2

Speaker 3 of 5
Michael N.G. James, University of Alberta, Canada
The Use of the Ascaris Pepsin Inhibitor, PI3, in the Design of Novel Peptide Inhibitors for Aspartic Proteinases

Wednesday, February 06 | 4:30PM - 7:00PM
Targeting Bacterial and Parasitic Proteinases
Room: Castle Peak 1-2

Speaker 4 of 5
James H. McKerrow, University of California, San Diego, USA
Parasite Proteases: New Insights into the Evolution, Diversity and Function of Cysteine Proteases

Wednesday, February 06 | 4:30PM - 7:00PM
Targeting Bacterial and Parasitic Proteinases
Room: Castle Peak 1-2

Speaker 5 of 5
Doron C. Greenbaum, University of Pennsylvania, USA
Short Talk: A Functional Proteomics Approach to Understand the Role of Cysteine Proteases in P.falciparum

Wednesday, February 06 | 5:40PM - 6:00PM
Coffee Break
Room: Castle Peak Foyer


Wednesday, February 06 | 7:00PM - 8:00PM
Welcome Mixer
Room: Castle Peak 3-4


Wednesday, February 06 | 7:00PM - 8:00PM
Cash Bar
Room: Castle Peak 3-4


Thursday, February 07 | 7:00AM - 8:00AM
Breakfast
Room: Castle Peak 3-4


Thursday, February 07 | 8:00AM - 11:00AM
Selected Aspects of Intracellular Proteolysis
Room: Castle Peak 1-2

Speaker 1 of 5
* Donald F. Steiner, University Of Chicago, USA
Proteolytic Processing in the Secretory Pathway

Thursday, February 07 | 8:00AM - 11:00AM
Selected Aspects of Intracellular Proteolysis
Room: Castle Peak 1-2

Speaker 2 of 5
Christine M. Debouck, Ardennes Biosciences LLC, USA
Application of Genomics to the Identification and Validation of Drug Targets

Thursday, February 07 | 8:00AM - 11:00AM
Selected Aspects of Intracellular Proteolysis
Room: Castle Peak 1-2

Speaker 3 of 5
Frank Uhlmann, Cancer Research UK London Research Institute, UK
The Proteolytic Mechanism of Chromosome Segregation

Thursday, February 07 | 8:00AM - 11:00AM
Selected Aspects of Intracellular Proteolysis
Room: Castle Peak 1-2

Speaker 4 of 5
Wolfgang P. Baumeister, Max Planck Institute of Biochemistry, Germany
The 26S Proteasome: A Supramolecular Complex Designed for Controlled
Proteolysis


Thursday, February 07 | 8:00AM - 11:00AM
Selected Aspects of Intracellular Proteolysis
Room: Castle Peak 1-2

Speaker 5 of 5
John W.M. Creemers, University of Leuven, Belgium
Short Talk: Identification of Physiological Substrates of Proprotein Convertases

Thursday, February 07 | 9:20AM - 9:40AM
Coffee Break
Room: Castle Peak Foyer


Thursday, February 07 | 4:00PM - 4:30PM
Coffee & Snacks Available
Room: Castle Peak Foyer


Thursday, February 07 | 4:30PM - 6:30PM
Challenges and Opportunities in Development of Proteinase In
hibitors as Therapeutics

Room: Castle Peak 1-2

Speaker 1 of 3
Wolfram Bode, Max Planck Institut, Germany
Crystal Structures of Proteinases: Tools for the Understanding of Substrate Specificity

Thursday, February 07 | 4:30PM - 6:30PM
Challenges and Opportunities in Development of Proteinase In
hibitors as Therapeutics

Room: Castle Peak 1-2

Speaker 2 of 3
Edwin L. Madison, USA
Transmembrane Serine Proteases in Cancer

Thursday, February 07 | 4:30PM - 6:30PM
Challenges and Opportunities in Development of Proteinase In
hibitors as Therapeutics

Room: Castle Peak 1-2

Speaker 3 of 3
Stefan Strobl, 4SC AG, Germany
Short Talk: Protein Structures - The Basis for in Silico Drug Design

Thursday, February 07 | 6:30PM - 7:30PM
Welcome Mixer
Room: Castle Peak 3-4


Thursday, February 07 | 7:30PM - 10:30PM
Entertainment
Room: Castle Peak 3-4


Thursday, February 07 | 7:30PM - 10:30PM
Cash Bar
Room: Castle Peak 3-4


Friday, February 08 | 10:26AM - 10:26AM
Departure


*Session Chair.