Chemical diversity, inherent

Another aspect of handling combinatorial chemicals versus natural products is tidiness. If one looks at a scatterplot of activity from an assay for combinatorial chemicals, the data look relatively tidy (Figure 1). TTie majority of samples demonstrate no appreciable activity, and it is not difficult to identify Wts. A scatterplot for natural product extracts in the same assay will show a broader range of activity (Figure 2). This breadth in assay response is proportional to the greater breadth of chemical diversity inherent in the natural product mixtures. It seems logical that the greater breadth of activity would be desirable, but this is frequently perceived to be an impediment because the HTS interpretative software is biased toward a one-to-one, sample-to-structure, system. 

The inherent complexity and chemical diversity of biomass predicts the recovery and purification of proteins from such a source will be an extremely challenging task. We have been studying this problem with a long-term research goal of identifying and establishing experimental conditions which may be applicable for protein purification from all biomass systems. 

Natural products have significant value. By definition, they are biologically compatible and relevant to cellular systems. Many are structurally rigid, making them inherently stable. They exhibit extremely broad chemical diversity. The number of natural products available is limited only by the ability to extract, purify and identify them. They clearly have a proven track record for provi ng novel pharmaceuticals, agrochemicals and medicines. For commercialisation purposes, their production is possible by fermentation and cultivation. With the advances made in molecular genetics, the modification of natural products is now possible via genetic, rather than strictly chemical, routes. 

All of these external resources have relied heavily on the university as a primary source. An unfortunate consequence of these activities over the past decade has been a depletion of the academic resources that have accumulated over the past 50 years. Furthermore, the availability of useful quantities from current academic research has become less likely as modern chemical techniques and instrumentation permit studies with only a few milligrams. This is especially apparent in the natural product field, as the unique diversity inherent in that group has placed such acquisition at a premium. Market demands, nevertheless, persist and have led to the emergence of synthesis factories that prepare compounds specifically for the screening market, using conventional chemical techniques. Output has been greatly enhanced at some of these centers by adoption of modular approaches in synthesis. These sources have helped to fill the void in numbers, but have done little to enhance the level of structural diversity or the cost factor. 

We have outlined the diversity and procedural flexibility afforded through the use of appropriately designed synthetic polymers for mammalian cell immobilization. Having selected the acrylate family of monomers because of their diversity, we have shown that mammalian cells may be microencapsulated in uncharged and polyelectrolyte polymer, in polyelectrolyte complexes and inside a cohesive precipitate from a destabilized emulsion all without significant loss of viability. Through this chemical diversity and inherent biocompatibility, these systems hold forth the possibility of improved transplantation therapies for a wide variety of cellular diseases. 

By means of modem computer technology, it is now possible to extract and handle structural information from large databases and thus, for this article, all STL structures were extracted from the Dictionary of Natural Products (rel. 10 2, 2002) and compiled into a database. This database contains the 2D structure of each of the 4861 STL based on the SMILES [7] formula (available as SDF file from the author on request). On grounds of the information inherent in these molecular structures it is now possible for the first time to characterise the basic chemical properties for the whole class of natural products and thereby to obtain new insights into their chemical diversity and the structural features underlying their biological activity. 

Phytochemistry has proven to be fertile ground for antifungal drug discovery [42] and promises to continue to do so given the inherent chemical diversity and relevance of the chemical defense mechanisms in plants in response to fungal infections [114]. An overview of the research in this area is presented as much of this work has been reviewed many times. 

Genetic modification Combined with the controlled structure and inherent chemical diversity, perhaps one of the most unique advantages of viral assemblies over man-made nanomaterials is the potential for further manipulation of the chemical functionalities at the genetic level. Specifically, efforts to confer precisely spaced chemical functionalities or to screen for desired affinities via introduction of amino acids and/or peptide screening (aka biopanning) have led to drastic expansions and new possibilities, and several seminal smdies are described here. 

Recently, Song et al. utilized a derivatization strategy to measure the broadest range of small molecule neurotransmitters reported to date, which included several amino acids, four monoamines, ACh, adenosine, and their major metabolites [54]. Due to the inherent chemical diversity and polar nature of these compounds, all the analytes, with the exception of ACh, were derivatized with benzyl chloride to achieve efficient separation in 8-minute run times by RPLC. Derivatization also improved the sensitivity of ESI—MS/MS analysis and provided a convenient way to generate isotope-labeled internal standards for quantification with commercially available C benzoyl chloride. The LC—MS method described in this study was suitable for the simultaneous detection of all analytes of interest in low-volume dialysis samples with sufficient sensitivity and high-throughput capability to permit fast sampling rates. 

The analysis of natural products in cosmetics is challenging. Extracts from terrestrial or marine sources are inherently complex and contain hundreds of individual components with a large chemical diversity. 

As was the case for petrochemicals, development of appropriate technology for the biorefinery will not occur immediately. It is critical to recognize that in comparison to fuels and power, chemicals and materials are, by far, the most technically complicated of the potential biorefinery outputs. The diversity inherent in chemicals and materials accurately reflects the nature of the chemical industry itself, anticipated to be the primary customer for any technology development. The fuels and power components are convergent, while the chemicals component is divergent (Figure 1). Importantly, this realization... 

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