Invited Lecture – Annemieke Madder

The talk will give an overview of our most recent achievements in the field of ligand and receptor design where conformational stabilization is key to success.

As a first example, the design and synthesis of so-called ‘frozen’ aptamers as small molecule receptors will be discussed. Introduction of imidazole modified nucleotide building blocks in a particular sequence context, allows for stabilization of the aptamer fold through non-covalent interstrand interactions.¹ Furthermore, efforts towards exploitation of our furanoxidation induced covalent interstrand crosslinking technology² for aptamer stabilisation will be discussed.

The second part of the talk will focus on our newly developed technology for the covalent restriction of peptide loop conformations onto non-peptide scaffolds. Several applications of the technology for the design of biologically active stabilized peptides will be discussed.³

Finally, the bottom-up design of an artificial receptor for medium-sized cyclodepsipeptides will be highlighted. Through a combination of careful design and modelling with experimental validation of binding affinity, we have developed a series of receptors for the food toxins Beauvericin and Cereulide.^[4] Applications in solid phase extraction of the toxins out of complex food matrices as well as the potential use of the artificial receptors as anti-dotes for Cereulide poisoning will be illustrated.

1. a) Buyst & Madder, Nucleic Acids Research, 2014, 43(1), 51; b) Op de Beeck & Madder, JACS, 2011, 133, 796; c) Verdonck, Madder & Martins, Nucleic Acids Research, 2018, 46(22), 11671.
2. a) Stevens, K.; Madder, A. Nucleic Acids Research, 2009, 1555; b) Op de Beeck, M. Madder A. JACS 2011, 133 (4), 796-807; c) Op de Beeck, M. Madder A. JACS, 2012, 10737.
3. Van Lysebetten & Madder, to be submitted.[4] Ornelis & Madder, Organic Letters, 2018, 20, 6368.