Mimicking the Biologically Active Part of the Cyclopeptides Segetalin A and B by “Clipping” of a Linear Tripeptide Derivative by Metal Coordination

Abstract

A new method for the conformational fixation of bioactive loop-type peptide structures is presented. Hereby, ligand moieties are attached to the termini of a linear peptide sequence. Upon metal complexation, a macrocyclic structure with a loop-type conformation of the peptide is formed. As a representative example, the preparation of a WAG-bridged dicatechol derivative is described which mimics the active part of the natural products Segetalin A and Segetalin B.

Abstract

(acac=acetylacetonate).

Keywords:

• Peptide coupling
• Cyclopeptide
• Coordination compound
• Segetalin

Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie. We thank Professor Dr M. Kappes and the Nanotechnology Institute, Forschungszentrum Karlsruhe for facilitating the ESI-MS measurements.

Notes

The Future of Supramolecular ChemistrySupramolecular chemistry is the “chemistry beyond the molecule”. Thus, during the last 30 years or so, research in the field of supramolecular chemistry has provided us with a large amount of information on non-covalently linked molecular architectures. Many complicated and, in some cases, aesthetically appealing structures have been reported, and we have learned how to specifically build up large structures which are sometimes comparable in size with nature's proteins or viruses. However, in the early days of supramolecular chemistry, the function of the supermolecule was important. Now that we have learned how to use non-covalent interactions, we have to focus more thoroughly on the function of the supramolecular aggregates. In our paper, we describe the use of metal complexation for a conformational fixation of a linear peptide in a cyclic structure. Hereby, we potentially transform an artificial inactive random-coil peptide into a biologically active cyclopeptide. In principle, we use a non-covalent interaction (metal coordination) to induce a specific biological function.Markus Albrecht was born in 1964 and studied Chemistry in Würzburg and Münster. He obtained his Dr rer. nat. in 1992 for his work on organometallic planar-tetracoordinate carbon compounds (research group of Professor Gerhard Erker). After one year as a postdoctoral fellow in the laboratories of Professor Kenneth N. Raymond in Berkeley (bioinorganic chemistry), he moved to the Institute of Organic Chemistry of the University of Karlsruhe and received his habilitation in 1997. His work on the metal-directed self-assembly of metallo-supramolecular aggregates was honoured with the “ADUC-Jahrespreis für Habilitanden”, and between 1998 and 2001, he was a Heisenberg-fellow of the DFG. In 2002, his teaching was awarded with the “Landeslehrpreis 2002 des Landes Baden-Württemberg”. Since spring 2002, he has been Professor of Organic Chemistry at the RWTH Aachen.