Prof. Dr. Norbert Sewald

Application of halogenases for the targeted introduction of halogen substituents
Halogenated aromatics, heteroaromatics and amino acids are promising building blocks for the synthesis and modification of peptides and proteins. Conventional synthetic strategies for halogenation often require harsh reaction conditions and a lack of selectivity in addition to molecular halogens. In contrast, enzymatic halogenation of tryptophan under mild conditions at room temperature in aqueous solution at pH 7 is regioselective even with free amino acids and in peptides/proteins without the formation of by-products, requiring only halide ions and O2 as stoichiometric agents. The use of enzymatic halogenation in preparative chemistry and for the modification of proteins was demonstrated for the first time.

Tumour targeting with the antimitotic agent cryptophycin
Cryptophycins, macrocyclic depsipeptides, have a cytotoxic effect even in the low picomolar range. Cryptophycin-1 exceeds the activity of the established chemotherapeutic agents paclitaxel and vinblastine by a factor of 100 to 1000 and shows activity against tumours that are resistant to multiple drugs. Following the successful development of total synthesis and modification of cryptophycins, various conjugates for tumour targeting were synthesised. For the synthesis of antibody-drug conjugates (ADC) and small molecule-drug conjugates (SMDC), the cryptophycin conjugates are conjugated to a homing device (antibody or peptide) via enzyme- or acid-labile linkers.

Isolation of natural substances from ethnomedicinally relevant plants or microorganisms
Plants, microorganisms or marine organisms offer an enormous supply of as yet undiscovered or uncharacterised natural substances that could potentially be used in therapy. In many cases, the therapeutic success of natural medicine is based on individual natural substances or combinations, e.g. in the form of extracts, whole plants or parts of plants. The aim of the work is to isolate new natural substances from plants or microorganisms that are native to African countries (Cameroon, Madagascar, Ethiopia) and are used there in various therapies, to elucidate their structure and to learn more about their mode of action.

Associate Editor of "Beilstein Journal of Organic Chemistry"
Member of the Advisory Board of "Journal of Peptide Science"