Vol.8 No.2A June 2003

IPK'2003

3rd International Conference Inhibitors of Protein Kinases

June 22-27, 2003

and Workshop

Phosphoryl-Transfer Mechanisms

June 27-28, 2003 Warsaw, Poland

DESIGN * STRUCTURAL BIOLOGY * PHOSPHORYLATION/ DEPHOSPHORYLATION PROCESSES * BIOCHEMISTRY * BIOTECHNOLOGY * SIGNALING PATHWAYS * CLINICAL ASPECTS * CHEMOTHERAPY

Volume 8 (2003) pp 503
Title PREFACE
Authors David Shugar
  This special number of Cellular & Molecular Biology Letters presents the Abstracts of Invited Lectures, and of submitted accepted Posters (some of which have been selected for oral presentation) to the 3rd International Conference on INHIBITORS OF PROTEIN KINASES (IPK'2003). Also included are Abstracts of lectures at an associated Workshop on Phosphoryl-Transfer Mechanisms.
Protein phosphorylation is widely recognized as the most important pathway for regulation of protein functions in living cells, by switching cellular activities from one state to another and, in this way, regulating gene expression, cell proliferation and cell differentiation. It is the major mechanism wherewith cells respond to extracellular signals such as hormones and growth factors, and controls all events at various stages of the cell cycle. Reversible protein phosphorylation is catalyzed by protein kinases and protein phosphatases.It has long been known that dysfunctions in activities of protein kinases may lead to severe pathological states. It is consequently not surprising that the biotechnology sector has for some time been devoting major efforts to “targeting” protein kinases for drug development, with considerable success in the past few years.
The foregoing led to organization, in September, 1998, in Warsaw, Poland, of the 1st International Conference on INHIBITORS OF PROTEIN KINASES (IPK'98), followed by publication of the texts of invited lectures, and of some posters selected for oral presentation, each in the form of an overview, in the international journal Pharmacology & Therapeutics 82, Nos. 2-3 (1999). Subsequent unabated progress in this field led, in turn, to the 2nd International Conference in Warsaw, September, 2001 (IPK'2001) devoted, as before, to real breakthroughs in identification and specificities of protein kinases, their three-dimensional structures and mechanisms of action, design and development of inhibitors, delineation of signaling pathways, in many instances with the aid of inhibitors, and numerous promising applications of inhibitors as therapeutic agents. Also included was a Workshop on Computer-Aided Drug Design, which attracted broader interest from participants than originally envisaged. The Proceedings subsequently appeared in Pharmacology &Therapeutics 99, Nos. 2-3 (2002).
The present 3rd International Conference (IPK'2003) has been extended somewhat in scope to include a special session on the newly developing field of protein kinases of pathogenic agents such as viruses, parasites and fungi, and their potential as therapeutic targets. It also includes a Workshop on Phosphoryl-Transfer Mechanisms, and relevance to protein kinases and protein phosphatases. It should be noted that, apart from being truly international in scope, IPK'2003 includes participation of leading specialists representing a broad range of disciplines from both Academia and the Biotechnology sector, thus ensuring adequate consideration of potential therapeutic applications.
Pdf Document [Rozmiar: 1332 bajtów]

Volume 8 (2003) pp 508-548
Invited Lectures
Abstracts List STRUCTURAL INSIGHTS INTO AGC-KINASE INHIBITOR BINDING FROM STUDIES WITH THE WORKHORSE PKA
Michael Gaßel, Christine B. Breitenlechner, Satur Herrero De Vega, Richard A.Engh and Dirk Bossemeyer - [Rozmiar: 1332 bajtów]p508

ANTISENSE PROTEIN KINASE A RI∂-INDUCED TUMOR REVERSION: PORTRAIT OF A MICROARRAY
Yoon S. Cho-Chung - [Rozmiar: 1332 bajtów]p510

PROTEIN KINASE SIGNALING CASCADE DURING NITRIC OXIDE-INDUCED APOPTOSIS, DEDIFFERENTIATION AND INFLAMMATORY RESPONSES OF ARTICULAR CHONDROCYTES
Jang-Soo Chun - [Rozmiar: 1332 bajtów]p512

INHIBITION OF HSP90 AS A SPECIAL WAY TO INHIBIT PROTEIN KINASES
Peter Csermely and Csaba Soti - [Rozmiar: 1332 bajtów]p514

THE KINETIC MECHANISM OF THE SERINE/THREONINE SPECIFIC PROTEIN KINASE ERK2
William F. Waas, Mark Rainey, Anna Szafranska and Kevin N. Dalby - [Rozmiar: 1332 bajtów]p516

STRUCTURE/FUNCTION STUDIES OF THE PHOSPHORYL-TRANSFER ENZYME: PHOSPHOENOLPYRUVATE CARBOXYKINASE
Louis T. J. Delbaere, Athena M. Sudom, Lata Prasad, Yvonne Leduc and Hughes Goldie - [Rozmiar: 1332 bajtów]p519

BACTERIAL SERINE AND TYROSINE PROTEIN KINASES CONTAINING A WALKER MOTIF
Josef Deutscher - [Rozmiar: 1332 bajtów]p522

PROTEIN KINASES AS TARGETS FOR ANTI-PARASITIC CHEMOTHERAPY
Christian Doerig - [Rozmiar: 1332 bajtów]p524

PROTEIN KINASE INHIBITORS AS ANTILEUKEMIC AGENTS
Doriano Fabbro - [Rozmiar: 1332 bajtów]p526

STRUCTURE, REGULATION AND FUNCTION OF PKB/AKT - A MAJOR THERAPEUTIC TARGET
Brian A. Hemmings - [Rozmiar: 1332 bajtów]p527

STRUCTURE-BASED DESIGN OF THE ANTITUMOR 2-HYDROXYARY-LIDENE-4-CYCLOPENTENE-1,3-DIONE TX-1123 AS A PROTEIN TYROSINE KINASE INHIBITOR HAVING LOW MITOCHONDRIAL TOXICITY
Hitoshi Hori, Hideko Nagasawa and Yoshihiro Uto - [Rozmiar: 1332 bajtów]p528

BIOSENSORS OF PROTEIN KINASE ACTION: FROM IN VITRO ASSAYS TO LIVING CELLS
David S. Lawrence - [Rozmiar: 1332 bajtów]p531

ADVANCES IN THE STRUCTURAL BIOLOGY, DESIGN AND CLINICAL DEVELOPMENT OF VEGF-R KINASE INHIBITORS FOR THE TREATMENT OF ANGIOGENESIS
Paul William Manley, Guido Bold, Gabrielle Fendrich, Pascal Furet, Jürgen Mestan, Thomas Meyer, Bernd Meyhack, Wilhelm Stark, Andre Strauss and Jeanette Wood - [Rozmiar: 1332 bajtów]p532

PHARMACOLOGICAL INHIBITORS OF CYCLIN-DEPENDENT KINASES (CDKS) AND GLYCOGEN SYNTHASE KINASE -3 (GSK-3)
Laurent Meijer - [Rozmiar: 1332 bajtów]p534

THE UL97 PROTEIN KINASE OF HUMAN CYTOMEGALOVIRUS (HCMV) AND HOMOLOGUES IN OTHER HERPESVIRUSES: RELEVANCE FOR VIRUS AND HOST
Detlef Michel and Thomas Mertens - [Rozmiar: 1332 bajtów]p535

VIRAL AND CELLULAR KINASES PLAY A CENTRAL ROLE IN VZV PATHOGENESIS AND ARE TARGETS FOR ANTIVIRAL KINASE INHIBITORS
Jennifer F. Moffat, Shannon L. Taylor and Stacey Leisenfelder - [Rozmiar: 1332 bajtów]p537

MOLECULAR DISSECTION OF FERTILISATION SIGNALLING WITH THE AID OF TYROSINE-KINASE-SPECIFIC INHIBITORS
Ken-ichi Sato, Tetsushi Iwasaki and Yasuo Fukami - [Rozmiar: 1332 bajtów]p541

EFFECTS OF PHARMACOLOGICAL CYCLIN-DEPENDENT KINASE INHIBITORS ON VIRAL TRANSCRIPTION AND REPLICATION
Luis M. Schang - [Rozmiar: 1332 bajtów]p543

cAMP-DEPENDENT PROTEIN KINASE: DYNAMICS OF CATALYSIS AND DOCKING
Susan S. Taylor, Pearl Akamine, Jerry Yang, Jian Wu, Ganesh Iyer, Ganesh Anand, Marat Valiev, John h. Weare and Donna D. Johnson - [Rozmiar: 1332 bajtów]p545

THE ROLE OF CYCLIN-DEPENDENT KINASE 5 IN BRAIN DEVELOPMENT AND DEGENERATION
Li-Huei Tsai - [Rozmiar: 1332 bajtów]p546

TYROSINE KINASE INHIBITORS AND ASTHMA
WS Fred Wong - [Rozmiar: 1332 bajtów]p548

   
abstracts of posters selected for oral presentations
Abstracts List DEVELOPMENT AND USE OF A PEPTIDE INHIBITOR OF THE C-JUN N-TERMINAL KINASE (JNK) SUBFAMILY OF MITOGEN-ACTIVATED PROTEIN KINASES
Marie A. Bogoyevitch, Renae K. Barr, Richard M. Hopkins, Paul M. Watt, Ingrid Boehm, Angela Chan and Peter G. Arthur - [Rozmiar: 1332 bajtów]p550

INHIBITORS OF Civ1 KINASE BELONGING TO 6-AMINOAROMATIC-2-CYCLOHEXYLDIAMINO PURINE SERIES AS POTENT ANTI-FUNGAL COMPOUNDS
Jean-Luc Haesslein, Paul Ferrari, Nathalie Jullian, Jacques Biton, Marie-Therese Bocquel, Christian Ciot, Anne-Marie Girard and Florence Bordon-Pallier - [Rozmiar: 1332 bajtów]p552

A STATISTICAL PROCEDURE (CHAIN) TO STUDY PROTEIN KINASE STRUCTURAL MECHANISMS
Natarajan Kannan and Neuwald Af - [Rozmiar: 1332 bajtów]p554

INSIGHTS INTO SELECTIVITY OF STI571 (Gleevec™) FROM X-RAY CRYSTALLOGRAPHY
Jacek Nowakowski, Vandana Sridhar, Devon A. Thompson, Ciarán N. Cronin, Daniel E. Vaughn, Anthony R. Gangloff, Bi-Ching Sang, Hua Zoa, Mark W. Knuth, Ronald V. Swanson, Gyorgy Snell, Clifford D. Mol, Keith P. Wilson and Duncan E. McRee - [Rozmiar: 1332 bajtów]p556

NEURONAL CYCLIN-DEPENDENT KINASE 5(CDK5) AND ITS SPECIFIC INHIBITOR (CIP): ITS PHYSIOLOGICAL AND PATHOLOGICAL ROLE IN THE NERVOUS SYSTEM
Yali Zheng, Sashi Kesavapany and Harish C. Pant - [Rozmiar: 1332 bajtów]p558

VALIDATION OF NOVEL PROTEIN KINASE TARGETS AND DEVELOPMENT OF NEXT GENERATION PROTEIN KINASE INHIBITORS USING ProQinase's INTEGRATED TECHNOLOGY PLATFORM PROTEIN KINASES
Christoph Sachsenmaier - [Rozmiar: 1332 bajtów]p561

STRUCTURE-BASED OPTIMIZATION OF CDK2 INHIBITORS
Martina Schäfer, Hans Briem, Thomas Brumby, Uwe Eberspächer, Michael Grimm, Martin Haberey, Holger Hess-Stumpp, Rolf Jautelat. Martin Krüger, Ulrich Lücking, Olaf Prien, Andreas Reichel, Gerhard Siemeister and Andreas Steinmeyer - [Rozmiar: 1332 bajtów]p562

BIFUNCTIONAL INHIBITORS OF PROTEIN KINASES FOR INTRACELLULAR APPLICATIONS
Asko Uri, Kaido Viht and Margus Pooga - [Rozmiar: 1332 bajtów]p564

COMBINING MEDICINAL CHEMISTRY WITH CHEMOGENOMIC AND COMPUTER-AIDED STRUCTURE-BASED DESIGN IN DEVELOPMENT OF NOVEL KINASE INHIBITORS
Michal Vieth, Harold B. Brooks, Chafiq Hamdouchi, William McMillen, Jason S. Sawyer, Jonathan M. Yingling and Faming Zhang - [Rozmiar: 1332 bajtów]p566

   
Posters
Abstracts List INHIBITION OF HYPOXIA-INDUCED TOLERANCE TO SUBSEQUENT HYPEROXIC INJURY IN LUNG CELLS BY PHOSPHATIDYL INOSITOL 3-KINASE INHIBITORS: LY294002 AND WORTMANNIN
Shama Ahmad, Aftab Ahmad, Evgenia Gerasmivoskaya, Kurt R. Stenmark and Carl W. White - [Rozmiar: 1332 bajtów]p570

AN INVESTIGATION OF CRK PROTEIN KINASES OF LEISHMANIA AND THE ASSESSMENT OF THEIR POTENTIAL AS DRUG TARGETS
Nahla Om Ali, Muntaser E. Ibrahim, Imadeldin E. Aradaib, Karen M. Grant and Jeremy C. Mottram - [Rozmiar: 1332 bajtów]p571

EVOLVING THE DESIRED COMPOUND PROFILE WITHIN AN LCK PROJECT
Ian R. Baldwin - [Rozmiar: 1332 bajtów]p573

CYCLIN-DEPENDENT PROTEIN KINASE-2 REGULATION BY PHOSPHORYLATION, A MOLECULAR DYNAMICS STUDY
Iveta Bártová, Michal Otyepka, Zdeněk Kříž and Jaroslav Koča - [Rozmiar: 1332 bajtów]p574

THE INHIBITION OF PROTEIN KINASE C BY HEPATITIS C VIRUS NON-STRUCTURAL PROTEIN 3 DEPENDS ON ITS CONFORMATIONAL STATUS
Peter Borowski and Philip Hartjen - [Rozmiar: 1332 bajtów]p576

EFFICIENT CHARACTERIZATION OF KINASE INHIBITORS USING LeadCodeTM TECHNOLOGY
Carsten Degenhart - [Rozmiar: 1332 bajtów]p578

THE PI3K KINASE INHIBITOR, LY294002, DECREASES RANTES-INDUCED PERITONEAL RECRUITMENT OF NEUTROPHILS IN MICE
Chiara Ferrandi, Hong Ji, Christian Rommel and Rocco Cirillo - [Rozmiar: 1332 bajtów]p579

CRYSTAL STRUCTURE OF AN ALTERED CATALYTIC SUBUNIT OF cAMP-DEPENDENT PROTEIN KINASE IN COMPLEX WITH THE PKC-KINASE INHIBITOR BISINDOLYL-MALEIMIDE 2 IN TWO DIFFERENT CONFORMATIONS-IMPLICATIONS FOR SELECTIVITY
Michael Gassel, Christine B. Breitenlechner, Richard A. Engh and Dirk Bossemeyer - [Rozmiar: 1332 bajtów]p582

INHIBITION OF C-JUN/JNK AND MLK PATHWAY ACTIVATION BLOCKS DNA DAMAGE-INDUCED DEATH IN EMBRYONIC CORTICAL NEURONS
Mohammad H. Ghahremani, Elizabeth Keramaris, Chantal Bazenet, Jonathan Ham, Ruth S. Slack and David S. Park - [Rozmiar: 1332 bajtów]p583

STUDY OF CASEIN KINASE II INHIBITORY ACTIVITY OF 4-AMINOQUINOLINE AND 4-AMINOQUINAZOLINE DERIVATIVES BY COMBINED DOCKING - MOLECULAR DYNAMICS APPROACH
Andriy G. Golub, Alexander O. Y. Yakovenko, Volodymyr G. Bdzhola and Sergiy M. Yarmoluk - [Rozmiar: 1332 bajtów]p584

HIGH-THROUGHPUT INTERACTION SCREENING FOR THE ELUCIDATION OF PROTEIN KINASE NETWORKS AND THE IDENTIFICATION OF PROTEIN KINASE INHIBITORS
Claudia Kruse, Sergey Vasiliev, Sabine Hanke and Hanjo Hennemann - [Rozmiar: 1332 bajtów]p585

EFFECT OF VARIOUS PROTEIN KINASE INHIBITORS ON OSMOTIC STRESS-ACTIVATED PROTEIN KINASE (OSAK) ACTIVITY Anna Kelner, Izabela Pękala and Grażyna Dobrowolska - [Rozmiar: 1332 bajtów]p586

NOVEL SMALL-MOLECULE INHIBITORS OF C-TERMINAL Src KINASE (Csk)
Anna Kilimnik, Maria N. Kostjukova, Ilya H. Pyatkin, Andrey M.Pronin, Svetlana R. Strelnikova, Yuri A. Fedotov and Alexander V. Kolesnikov - [Rozmiar: 1332 bajtów]p588

TYROSINE PHOSPHATASE SHP-1 REGULATES LPS-INDUCED CYTOKINE NETWORKS INVOLVED IN INFLAMMATION
Chinonso Okenwa, Dorothy Rego, Natalie J. Pang and Maya Kozlowski - [Rozmiar: 1332 bajtów]p590

THEORETICAL STUDIES ON SUGAR AND PROTEIN KINASES: STRUCTURAL AND MUTATIONAL VARIABILITY
Jacek Kuśka and Jacek Leluk - [Rozmiar: 1332 bajtów]p592

COMPARATIVE STUDIES OF SUGAR AND PROTEIN KINASES: GENETIC RELATIONSHIPS AND CONSENSUS SEQUENCES
Anna Zdyb and Jacek Leluk - [Rozmiar: 1332 bajtów]p593

IMPROVING THE EFFICIENCY OF HALOGENATED BENZIMIDAZOLE INHIBITORS OF PROTEIN KINASE CK2
Flavio Meggio, Mario A. Pagano, Mariola Andrzejewska, Luca Cesaro, Zygmunt Kazimierczuk and Lorenzo A. Pinna - [Rozmiar: 1332 bajtów]p594

TETRASUBSTITUTED PURINES AS INHIBITORS OF CDK1
Jiří Moravec, Libor Havlicek, Daniela Moravcova, Jan Hanus, Květoslava Fuksova, Michal Otyepka, Vladimír Krystof and Miroslav Strnad - [Rozmiar: 1332 bajtów]p596

RATIONAL DESIGN OF NEW COMPETITIVE INHIBITORS OF HUMAN CK2 ACTIVITY
Stefano Moro, Diego Dal Ben, Giuseppe Zagotto, Flavio Meggio, Stefania Sarno and Lorenzo A. Pinna - [Rozmiar: 1332 bajtów]p598

DEVELOPING KINASE TOOLS FOR DRUG DISCOVERY
Steve Davies, Andrew Paterson, Joachim Morr, Barry Ewen, Chris Armstrong and Sue Dale - [Rozmiar: 1332 bajtów]p599

STRUCTURAL GENOMICS OF THE HUMAN PROTEIN KINASE FAMILY
Anna Aparicio, Alexei Brooun, Ellen Chien, Ellen Chi, Bernard Collins, Ciarán N. Cronin, Anthony Davies, Douglas Dougan, Erin Heien, Mark Hilgers, David Hosfield, Marie Hu, Daniel Kassel, Stella Kim, Mark W. Knuth, Michelle Kraus, Irena Levin, Kheng Lim, Melinda Manuel, Duncan E. Mcree, Clifford D. Mol, Jacek Nowakowski, Joe Rogers, Bettina Roth, Bi-Ching Sang, Daniel Scheibe, Robert Skene, Vandana Sridhar, Ronald V. Swanson, Devon A. Thompson, Darbi Witmer, Robert Wynands, Gyorgy Snell, Keith P. Wilson, Garret Textor, Daniel Vaughn, Sheng Ye and Hua Zoa - [Rozmiar: 1332 bajtów]p600

WP744, A NOVEL HIGHLY APOPTOTIC AND ANTI-PROLIFERATIVE AGENT AGAINST STI-571-RESISTANT LEUKEMIC CELLS
Waldemar Priebe, Gilad Evrony, Izabela Fokt, Sangyou Lee, Moshe Talpaz and Nicholas J. Donato - [Rozmiar: 1332 bajtów]p601

SCC DFT-TB ENERGY CALCULATIONS OF THE PHOSPHORYL TRANSFER REACTION IN THE PKA ACTIVE SITE
Franciszek Rakowski, Pawel Grochowski and Bogdan Lesyng - [Rozmiar: 1332 bajtów]p603

PEPTIDE MICRO-ARRAYS FOR KINASE PROFILING
Mike Schutkowski, Ulf Reimer, Sören Panse, Liying Dong and Jens Schneider-Mergener - [Rozmiar: 1332 bajtów]p605

STUDIES ON CK2 INHIBITION CAPACITY OF 4-AMINOQUINOLINES AND 4-AMINOQUINAZOLINES
Natalia M. Ryabchenko, Olexandr G. Kukharenko, Vadim M. Sapelkin, Galina G. Dubinina, Svetlana Y. Dmitrieva and Sergiy M. Yarmoluk - [Rozmiar: 1332 bajtów]p606

INHIBITION OF A Ca2+-DEPENDENT PROTEIN KINASE FROM IRANIAN RICE LEAVES BY pH AND TEMPERATURE
Reyhaneh Sariri and Amir Arasteh - [Rozmiar: 1332 bajtów]p607

EFFECTS OF PROTEIN KINASE A INHIBITOR (H-89) ON SPATIAL MEMORY AND EXPRESSION OF CHOLINE ACETYLTRANSFERASE (ChAT) AND VESICULAR ACETYLCHOLINE TRANSPORTER (VAChT) PROTEINS
Mohammad Sharifzadeh, Kurdastan Sharifzadeh and Mohammad H. Ghahremani - [Rozmiar: 1332 bajtów]p609

TOPBUILDER-MOLECULAR TOPOLOGY BUILDING AND CHEMICAL DATABASE PROCESSING SOFTWARE
Alexander O.Y. Yakovenko, Andryi G. Golub, Volodymyr G. Bdzhola and Sergiy M. Yarmoluk - [Rozmiar: 1332 bajtów]p610

YEAST Cu,Zn-SUPEROXIDE DISMUTASE (SOD) AS AN INHIBITORY SUBUNIT OF PROTEIN KINASE CK2
Rafał Zieliński, Olga Abramczyk, Piotr Zień, Marek Pilecki, Konrad Kubiński, Ulf Hellman and Ryszard Szyszka - [Rozmiar: 1332 bajtów]p611

SELECTIVITY OF 4,5,6,7-TETRABROMOBENZIMIDAZOLE (TBBZ) AS AN ATP-COMPETITIVE POTENT INHIBITOR OF PROTEIN KINASE CK2 FROM VARIOUS SOURCES
Piotr Zień, Maria Bretner, Katarzyna Zastąpiło, Ryszard Szyszka and David Shugar - [Rozmiar: 1332 bajtów]p613

   
Workshop on phosphoryl-transfer mechanisms
Abstracts List PATHWAYS AND PROTONATION STATES IN THE MECHANISM OF PROTEIN TYROSINE PHOSPHATASE: A STUDY USING COMBINED MACROSCOPIC AND QUANTUM-MECHANICAL MODELS
Dilipkumar Asthagiri, Valerie Dillet, Tiqing Liu, Louis Noodleman, Robert L Van Etten and Donald Bashford - [Rozmiar: 1332 bajtów]p616

QUANTUM AND QUANTUM-CLASSICAL STUDIES OF PHOSPHORYL-TRANSFER MECHANIMS IN MODEL SYSTEMS
Paweł Grochowski - [Rozmiar: 1332 bajtów]p617

SIMULATIONS OF STRUCTURE AND DYNAMICS OF PHOSPHOLAMBAN: INFLUENCE OF ENVIRONMENT AND OF PHOSPHORYLATION
Krzysztof Kuczera and Yao Houndonougbo - [Rozmiar: 1332 bajtów]p619

A COMPARATIVE STUDY OF THE PRIMARY STRUCTURES OF PROTEIN AND SUGAR KINASES
Jacek Leluk and Bogdan Lesyng - [Rozmiar: 1332 bajtów]p620

COMPUTATIONAL STUDIES ON ENZYMATIC PHOSPHATE HYDROLYSIS
Jordi Villa - [Rozmiar: 1332 bajtów]p622

THE MECHANISM OF ADP PHOSPHORYLATION BY ATP SYNTHASE
Joachim Weber - [Rozmiar: 1332 bajtów]p623

MODELS FOR BIOLOGICAL PHOSPHORYL TRANSFER
Nicholas H. Williams - [Rozmiar: 1332 bajtów]p624