of novel chemo- and biocatalytic combinatorial libraries which will be screened
for biological activities (e.g. as antibacterial or anticancer agents);
of new polymers for polymer supported synthesis in aqueous or organic media;
of improved enzymatically cleavable linkers for release of target compounds
in aqueous medium for easier screening methods;
evolution of the enzymes used to improve yields and selectivity of release
of enzymes and whole cells for combinatorial regio- and stereoselective biotransformations
to introduce new functionalities and groups to mimic natural evolution.
of the work:
The spread of antibiotic resistance in disease-causing bacteria poses serious
problems for the control of both old and new diseases. In the recent years macrocyclic
compounds such as epothilone, rifamycin, vancomycin gain increasing importance
as more specific drugs in antibiotic (antibacterial, antifungal etc.) and anti-cancer
therapy. Active compounds contain common principles which can be used as bases
for new lead compound discovery.
The present proposal aims at the synthesis of a new generation of anti-infective
and anti-cancer compounds by designing and producing novel compound libraries
by orchestration of polymer-supported combinatorial bio-/chemistry, together
with novel strategies for screening those libraries with an "intelligent"
The work will include:
of novel methodologies for reactions on support together with a new class
of enzymatically cleavable linkers and tailor-made enzymes for this purpose.
of defined macroporous polymer particles suitable for biocatalysis and of
new functional polymers, both being compatible both with water and organic
design of therapeutic agents by use of natural compounds libraries and chemical
of enzymes, whole cells and crude extracts for a biocatalytic combinatorial
approach offering the opportunity to combine functionalities in target structures
which are difficult to obtain by traditional chemical methods.
and automated drug core modification, screening and analysis.
engineering to gain information for de-bottlenecking for scale up and scale
polymers for polymer supported synthesis together with novel (enzymatically
cleavable) linkers and genetically engineered enzymes for enzymatic release;
(enzymes, cell extracts, building blocks) for combinatorial biocatalysis;
and biocatalytic combinatorial libraries containing novel functionalities;
lead structures for therapeutics by automated core substance modification
system and innovative screening systems with intelligent linkers.