Bioactive Agents from Natural Sources: Trends in Discovery and Application - Advances in Biochemical Engineering Biotechnology - page 141

For increasing effectivity and decreasing costs for HTS technologies,the basic
limiting factor for finding new lead compounds will be the supply of structural
diversity.The relevance of natural products in drug discovery and development
will consequently depend to a great extent on the efficiency and costs of accesss
to chemically diverse extracts from natural sources compared to the supply from
synthetic sources [360].
6.2
Technologies
Currently, dramatic changes in drug discovery technologies are taking place
affecting any issue that plays a role in the lead-finding process.In future,target
elucidation will probably derive mainly from genomic sciences,although lines
of argumentation are arising that stress the relevance of target gene finding
starting from given bioactive agents performing valuable in vivo activity.
Progress in lead discovery is expected to depend substantially on methods and
techniques that accelerate validation of new target genes potentially related to
human disorders.Validation can be provided either by functional gene expres-
sion in valid animal models, or by immediate transfer to HTS in order to get
rapid access to a low-molecular mass effector that gives rise to both a drug can-
didate and target validation.
Today,limitations in HTS are not only due to missing high quality test sample
numbers but also due to quantitative limitations in the availability of target
reagents.In order to compensate for the shortcomings in target supply further
progress mainly in heterologous gene expression is required, either towards
advanced cell-based assays or towards target isolation and application in a defi-
ned molecular system.
Acknowledgement. The authors would like to thank Dr.Kai U.Bindseil (AnalytiCon AG,Berlin)
for valuable help for Sect. 4.2.1 “Combinatorial Natural Product Chemistry”, and Dr. Isabel
Sattler (HKI,Jena) for Sect.4.2.2 “Biological Derivatization Methods”.
7
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