26 No. 6
by David StC. Black
The 7th International Symposium on Biomolecular Chemistry—ISBOC-7—was held at the University of Sheffield from 27 June to 1 July 2004. The first thing to note is that the previous descriptor in the title, namely “Bioorganic” was deliberately replaced by the word “Biomolecular,” in order to broaden the scope and allow the introduction of “bioinorganic” chemistry. This series of conferences is planned by the Biomolecular Subcommittee of the IUPAC Division of Organic and Biomolecular Chemistry. The conference was master-minded by Michael Blackburn and his committee, in collaboration with the Royal Society of Chemistry, and by all measures was a great success.
The key ingredient in any conference is high-quality scientific content. The approximately 250 participants were given a veritable feast of stimulating and informative plenary and invited lectures, and they joined in many vigorous and stimulating discussions. The statistics show that there were 7 plenary, 5 keynote, and 23 invited lectures, 38 contributed oral presentations, and 86 poster presentations. The posters were on display for the entire duration of the symposium, and extended lunch and tea breaks allowed generous time for discussion.
Biomolecular chemistry is arguably the most important area of chemistry for development during this century, as it deals with fundamental questions relating to the controlling mechanisms of life itself. The scene was set in the opening lecture, the Alexander Todd Lecture, sponsored by Yusuf Hamied of Cipla Ltd. (Bombay and London), and delivered by George Whitesides (Harvard University, USA), who dealt with both the fundamental and applied aspects of biomolecular chemistry. Whitesides spoke of the need to understand the fundamental nature of the cell as a system of chemical reactions, and the shift in emphasis in biology from structure to function, leading for example to important research on protein-ligand interactions, which by their floppy nature are still beyond the accuracy of modelling techniques.
Moving to the applied area of the pharmaceutical industry, practicalities such as cost become highly significant, and change will be needed in planning future drug development. Polyvalency is a promising approach, and genomics provides a new tool, but new assays will need to be simple and inexpensive, if costs are to be contained. The current state of structure-based drug discovery was outlined by Hans-Joachim Böhm (Roche, Basel, Switzerland), who showed that computational prediction of binding affinities have led to enhanced hit rates.
The University of Sheffield Krebs Lecture was given by Stephen Lippard (MIT, USA), whose bioinorganic research is aimed towards an understanding of the biological oxidation of hydrocarbons at non-heme diiron centres, and to the development of practical synthetic models that will achieve the same thing in vitro. The theme of mixed-valent iron systems was developed further by Carl Wieghardt (Mülheim, Germany) and James Cowan (Ohio State University, USA). The bioinorganic theme was neatly linked back into a major bioorganic area by Bengt Nordén (Chalmers University, Gothenburg, Sweden) in a lecture on the role of binuclear ruthenium intercalators in the study of DNA binding mechanisms, which emphasised the importance of kinetic rather than thermodynamic recognition.
Dieter Seebach (ETH, Zürich, Switzerland) brought us up to date with the exciting new properties of oligomers from homologated proteinogenic amino acids. In only eight years, the enormous amount of synthetic work required has been more than repaid by the results. The critical tertiary structural motifs occur in smaller oligomers than for the proteins, and consequently these oligomers are a practical prospect for diagnostic and pharmaceutical applications.
The role of real proteins in enzymes was the subject of the lecture on dihydrofolate reductases by Stephen Benkovic (Penn State University, USA), which brought all the armory of physical organic chemistry to bear on the understanding of conformational changes which are responsible for function. Dudley Williams (Cambridge, UK) advanced the hypothesis that increasing hydrogen bonding results in the strengthening of existing ones and leads to significant lowering of ligand-protein binding energies. All the leading experts then participated in a remarkably lively and extended discussion on the possible novelty and validity of this hypothesis. Those graduate students present will look back on this discussion in years to come and realise its significance.
Further research on enzymatic transition state structures was described by Vern Schramm (Albert Einstein College of Medicine, New York, USA) on N-ribosyltransferases: the design of new drugs can be advantageously based on matching the transition state structure. Using a combinatorial screening approach, enzymes can be evolved to provide mutants which can show enhanced enantioselectivity in reactions that are valuable for synthetic organic chemistry. Manfred Reetz (Mülheim, Germany) has developed this technique and shown that even more exciting applications lie ahead. Experimental evidence emphasises that enantioselectivity arises in the dynamic reaction process, and not as a result of the fit of the substrate or product.
Just one dramatic example of the rapid progress being made in dealing with large biological macromolecules was illustrated in the lecture by Carol Robinson (Cambridge, UK), who explained how mass spectrometry can now be used to learn about interactions between intact proteins and small molecules. The use of nano-electrospray mass spectrometry has allowed the molecular mass measurement of several ribosymes, which are composed of three very large RNA molecules and over 50 different proteins.
The scope of the conference was sufficiently broad to include lectures on the biological impact of small RNAs (Kazunari Taira, Tokyo, Japan) and synthetic multifunctional pores (Stefan Matile, Geneva, Switzerland).
The overall framework of the conference grouped the oral and poster presentations into six symposia, on proteins and peptides, bioinorganic chemistry, synthetic and bioorganic chemistry, structure and mechanism, biothermodynamics, and biospectroscopy. The posters were available for most of the conference and relaxed coffee and lunch breaks provided ample opportunity for discussion of them. In addition to an excellent conference banquet in the historic Cutlers Hall, a special feature of the social program was a piano recital by the internationally-renowned local pianist Benjamin Frith on the Bosendorfer Imperial grand piano in the Firth Hall of Sheffield University.
ISBOC-8, the next conference in this exciting—and increasingly important—series, will be held in approximately two years’ time in Florida, USA, chaired by Russell Kerr.
David StC. Black <[email protected]> was IUPAC representative at the ISBOC-7. He is now IUPAC Secretary General, and has been a member of the IUPAC Division of Organic and Biomolecular Chemistry since 1994. He is professor at the University of New South Wales, in Sydney, Australia.
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