The conformation of cyclo(-D-Pro-Ala4-) as a model for cyclic pentapeptides of the DL4 type

The conformation of the cyclic pentapeptide cyclo(-D-Pro-Ala(4)-) in solution and in the solid state was reinvestigated using modern NMR techniques. To allow unequivocal characterization of hydrogen bonds, relaxation behavior, and intramolecular distances, differently labeled isotopomers were synthesized. The NMR results, supported by extensive MD simulations, demonstrate unambiguously that the preferred conformation previously described by us, but recently questioned, is indeed correct. The validation of the conformational preferences of this cyclic peptide is important given that this system is a template for several bioactive compounds and for controlled "spatial screening" for the search of bioactive conformations.     

N-methylated cyclic pentaalanine peptides as template structures

The N-methylation of cyclic peptides can be used to modify the activity and/or selectivity of biologically active peptides. As N-methylation introduces different flexibility and lipophilicity, it can also improve the bioavailability (the ADMET profile). To search for conformationally constrained cyclic peptides, a library of 30 different N-methylated peptides with the basic sequence cyclo(-D-Ala-L-Ala4-) was synthesized. Based on the NMR analysis, seven of these peptides exhibited single conformations (>98%). The structural features of these peptides were determined by a combination of NMR and distance geometry and then further refined by molecular dynamics simulations in an explicit DMSO solvent box. The structures provided from these efforts can now serve as templates for the rational design of cyclic pentapeptides with a distinct backbone conformation or for "spatial screening" to explore the bioactive conformation of medically important peptide systems.     

TiO2 nanotubes: photocatalyst for cancer cell killing

The present work reports on the use of self‐organized TiO₂ nanotube layers for the photocatalytic killing of cancer cells. TiO₂ nanotube layers with different dimensions (diameter 50 nm and 100 nm, thickness 800 nm and 1.3 μm, respectively) were grown by anodization of Ti. Upon low dose of UV irradiation, the vitality of cancer cells cultured on these nanotube layers was significantly affected – the cells reduced their shape and size and a significant amount of the dead cells was found. These results demonstrate that self‐organized TiO₂ nanotube layers can be used for photo‐induced cancer cell killing. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)