Molecular Aspects of Chemotherapy : Proceedings of the Third International Symposium on Molecular Aspects of Chemotherapy Gdańsk, Poland June 19-21, 1991

While serendipity and random screening continue to fulfil a significant role in the search for new drugs, current remarkable advances in molecular biology and genetics are dictating to a profound extent the approaches employed in their development. Increasing attention is being devoted to investigations of the mechanisms of action of existing drugs, and the sources of undesired side effects, at the molecular level. The information so derived is now extensively applied, with the aid of broad inter­ disciplinary approaches, both theoretical and experimental, to improvements in existing drugs, and the rational design of new ones. The foregoing comprised the subject matter of the 3rd Inter­ national Symposium on "Molecular Aspects of Chemotherapy", under the auspices of the International Society of Chemotherapy, and organized by the Committee on Drug Research, Polish Academy of Sciences, and the Department of Biotechnology and Biochemistry, Technical University of Gdansk. This volume includes the texts of the review lectures presented by invited participants on up-to-date achievements, and future perspectives, in molecular mechanisms of inhibition of cellular functions and metabolism, with emphasis on the design and mechanisms of action of chemotherapeutic agents for treatment of bacterial, neoplastic, viral and parasitic diseases. From the Contents, it will be seen that the range of disciplines represented was a broad one, including theoretical and experimental chemists, physicists, molecular biologists, biochemists, enzymologists, virologists, tumour biologists. Plenary sessions were supple­ mented by several poster sessions. Front Matter....Pages I-VIII Insight into Lactam Antibiotics and their Receptors from Computational Chemistry....Pages 1-22 New Methods in Molecular Shape Analysis to Identify and Characterize Active Conformations....Pages 23-40 Molecular Mechanisms for the Sequence Recognition of DNA by (+)-CC-1065....Pages 41-54 A Common Structural Pattern among Many Biologically Active Compounds of Both Natural and Synthetic Origin — A Novel Approach to the Design of Antineoplastic Agents....Pages 55-71 Cyclic Nucleotide Metabolism as a Target in Chemotherapy....Pages 73-104 Resistance to Anthracyclines in Multidrug Resistant Cells. Role of the Membrane Transport....Pages 105-117 Tumor Necrosis Factor: Mechanism of Action and its Potential for Anticancer Therapy....Pages 119-125 Exploitation of Peptide Transport Systems in the Design of Antimicrobial Agents....Pages 127-142 Inhibitors of 2,3-Oxidosqualene-Lanosterol Cyclase as Antifungal Agents....Pages 143-152 The Use of the 3-Dimensional Structures of Rhinoviruses in the Design of Antiviral Agents....Pages 153-162 Design of Virus-Specific Inhibitors of Terminal Glycosylation Enhancing the Antigenicity of Viral Glycoproteins....Pages 163-171 Comparison of Crystal Structures of Inhibitor Complexes of the Human Immunodeficiency Virus Protease....Pages 173-186 Anti-HIV Agents Interfering with the Viral gp120-Cellular CD4 Interaction....Pages 187-208 Polyionic Compounds Selectively Alter Availability of CD4 Receptors for HIV Coat Protein rgp 120....Pages 209-217 Penciclovir and Famciclovir, Selective Anti-Herpesvirus Agents....Pages 219-230 2′3′Dideoxy-3′Thiacytidine (SddC) as an Anti-Human Hepatitis B Virus (HBV) and Anti-Human Immunodeficiency Virus (HIV) Agent....Pages 231-238 Phosphorylating Enzymes Involved in Activation of Chemotherapeutic Nucleosides and Nucleotides....Pages 239-270 Back Matter....Pages 271-279 This volume comprises the texts of the plenary lectures at the 3rd International Symposium on "Molecular Aspects of Chemotherapy"(Gdansk, Poland, June 19-21,1991), with up-to-date accounts of current multidisciplinary approaches, both theoretical and experimental, in the development of chemotherapy of bacterial, neoplastic, viral and parasitic diseases. It includes procedures for the design of new chemotherapeutic agents, based on mechanisms of action of existing ones, and selection of defined targets, leading to improved procedures for rational design of new drugs. Specific topics covered embrace the use of molecular dynamics simulations of mechanisms of action of lactam antibiotics. QSAR analyses of intercalating and other types of antitumor drugs; applications of 3-dimensional structures of rhinoviruses inthe design of antiviral agents; the mode of action and future perspectives, of Tumor Necrosis Factor; virus-specific inhibitors of glycosylation; mechanisms of action of some anti-AIDS agents, including structures as a potential target in antitumour and antiviral chemotherapy; role of phosphorylating enzymes involved in "activation" of chemotherapeutically active nucleoside analogues