Biomedical Engineering Reference
In-Depth Information
carbohydrate chemistry this concept of reconstituting a pathway or a com-
bination of interlinked pathways has found many interesting applications
[318, 319]. A new and powerful application for enzymes as catalysts in
synthetic chemistry are combinatorial strategies for the generation ofwhole
libraries of organic compounds [320, 321]. Enzymes are able to catalyze
specific conversions of mixtures of complex molecules in solution under
mild conditions and without by-products. Up to now, the applicability of
combinatorial biocatalysis has been shown on an array of structurally
diverse organic molecules. A library of nearly 200 analogs allowed to
identify acylated derivatives ofpaclitaxel that overcome solubility problems
by a 58-fold (paclitaxel 2
-
adipic acid) increase in relative water solubility [322]. As an example the
derivatization program performed on the natural product bergenin by a
two-staged protocol is depicted (Fig.12) [320,321].
¢
-adipoylglucose) and a 1625-fold (paclitaxel 2
¢
5
Developments in Drug Discovery Technologies
5.1
Potential Impact of Genomic Sciences
All drugs that are currently on the market - excluding antiinfectives - can be put
down to 417 different disease related human targets comprising primarily
G-protein-coupled receptors,enzymes,hormones,growth factors,ion channels,
and other biomacromolecules [3].It is obvious that today most diseases cannot
be cured. This may implicate that the corresponding disease targets so far
known give access to good drugs only in a few cases.However,some targets such
as the angiotensin-converting enzyme or the adrenergic receptor subtypes may
be close to ideal targets,as drugs affecting these targets represent highly effec-
tive and safe antihypertensive therapeutics [3].
On the other hand,about 33% of the today's drug targets are related to neu-
rological disorders without realizing satisfying therapeutic approaches to any of
the serious neurodegenerative diseases. The conclusion drawn in pharmaceu-
tical industry from this fact is quite remarkable.It is not assumed that further
screening ofcompounds could result in an optimized drug.On the contrary,it is
expected that improved therapy is only accessible by identifying and affecting
new targets.These new disease related targets can be approached by structural
and functional analysis of the human genome. Therefore, genomic sciences
actually have become a key issue in order to accelerate drug discovery and devel-
opment in future.
Currently,research in the pharmaceutical industry is concentrated on about
100 diseases that in their opinion really matter.In order to calculate how many
targets may refer to these diseases of interest the following is estimated from
diseases with well understood pathways such as diabetes type II and hyper-
tension [3]:Most diseases are caused by genetic factors,and proved to be multi-
factorial. The number of genes involved to contribute to the various disease
phenotypes turned out to be around five to ten, thus resulting in 500 to 1,000
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