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321.
Arnar Sigurdsson Dr. Berta M. Martins Dr. Simon A. Düttmann Martin Jasyk Benjamin Dimos-Röhl Felix Schöpf Manuel Gemander Dr. Caroline H. Knittel Dr. Romina Schnegotzki Bianca Schmid Dr. Simone Kosol Lea Pommerening María Gonzáles-Viegaz Maria Seidel Manuela Hügelland Prof. Dr. Silke Leimkühler Prof. Dr. Holger Dobbek Dr. Andi Mainz Prof. Dr. Roderich D. Süssmuth 《Angewandte Chemie (International ed. in English)》2023,62(23):e202302490
Lanthipeptides are ribosomally-synthesized natural products from bacteria featuring stable thioether-crosslinks and various bioactivities. Herein, we report on a new clade of tricyclic class-IV lanthipeptides with curvocidin from Thermomonospora curvata as its first representative. We obtained crystal structures of the corresponding lanthipeptide synthetase CuvL that showed a circular arrangement of its kinase, lyase and cyclase domains, forming a central reaction chamber for the iterative substrate processing involving nine catalytic steps. The combination of experimental data and artificial intelligence-based structural models identified the N-terminal subdomain of the kinase domain as the primary site of substrate recruitment. The ribosomal precursor peptide of curvocidin employs an amphipathic α-helix in its leader region as an anchor to CuvL, while its substrate core shuttles within the central reaction chamber. Our study thus reveals general principles of domain organization and substrate recruitment of class-IV and class-III lanthipeptide synthetases. 相似文献
322.
Dieter Wöhrle Maria Shopova Jörg G. Moser Holger Kliesch Ulrike Michelsen Silke Müller Andrea Weitemeyer 《Macromolecular Symposia》1996,105(1):127-138
Different possibilities of macromolecular metal complexes as photosensitizers (PS) for their potential use in the photodynamic therapy of cancer are described. The prepared metal porphyrazin derivatives (metals: Zn(II), Si(IV)(X)2) exhibit long wavelength absorption and high singlet oxygen quantum yields under irradiation. One possibility is the incorporation of the PSs in liposomal vesicles giving hydrophobic conjugates with low densitiy proteins in the serum after injection. Good tumor accumulation and photodynamic activities are observed. Increased tumor uptake is also known for Pcs covalently connected via the ligand to poly(ethylene glycol monomethyl ether). New compounds contain the hydrophilic polymer at axial substituents of Si(X)2Pc and Si(X)2Nc. Some newly synthesized compounds with only one functional group exhibit the possibility of coupling to macromolecules like e.g. monoclonal antibodies. 相似文献