Luka Raguz

Luka Raguz

Email: luka.raguz@leibniz-hki.de

Modular synthetic approaches towards natural sphingoid base-type signaling molecules

Sphingoid bases and sphingolipids are essential multifunctional cellular compounds, which serve not only as integral components of cell membranes, but also as essential regulatory signals for fundamental cellular processes. They were first thought to exist exclusively in eukaryotes, but have now been repeatedly identified and isolated from important bacterial and viral sources. Despite being abundant signaling molecules, the biological function of many sphingolipid derivatives remains elusive.

Prominent examples of fungal origin are sphingofungins and myriocin (ISP-1), which exhibit antifungal activity in the picomolar to nanomolar range. Their discovery has led to the development of many pharmaceutical drug leads (e.g. FTY720 and safingol. But the intrinsic biological role of sphingofungins is unknown until to date. In another study bacterial sulfonolipids, such as RIF-1 and RIF-2, regulate an onset of development in one of the closest living relatives of animals, the choanoflagellate Salpingoeca rosetta. A structural analog IOR-1 inhibits partially the activity of RIF molecules.

Due to their intrinsic biological function of these types of molecules, this research project will focus on efficient and new synthetic strategies towards of rare microbial sphingoid base-type signaling molecules to allow their detailed functional analysis.

Publications

Roman D, Raguž L, Keiff F, Meyer F, Barthels F, Schirmeister T, Kloss F, Beemelmanns C (2020) Modular Solid-Phase Synthesis of Antiprotozoal Barnesin Derivatives. Org Lett , Details PubMed

Guo H, Schmidt A, Stephan P, Raguž L, Daniel Braga D, Kaiser M, Dahse HM, Weigel C, Lackner G, Beemelmanns C (2018) Precursor-directed Diversification of Cyclic Tetrapeptidic Pseudoxylallemycins. Chembiochem 19(21), 2307-2311. Details PubMed

Rischer M, Raguž L, Guo H, Keiff F, Diekert G, Goris T, Beemelmanns C (2018) Biosynthesis, Synthesis, and Activities of Barnesin A, a NRPS-PKS Hybrid Produced by an Anaerobic Epsilonproteobacterium. ACS Chem Biol 13(8), 1990-1995. Details PubMed

Leichnitz D, Raguž L, Beemelmanns C (2017) Total synthesis and functional analysis of microbial signalling molecules. Chem Soc Rev 46(20), 6330-6344. Details PubMed

Supervisor

Christine Beemelmanns

Start of PhD

August 1, 2016

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