Peptides derived from non-ribosomal peptide synthetases (NRPSs) represent an important class of pharmaceutically relevant drugs. Methods to generate novel non-ribosomal peptides or to modify peptide natural products in an easy and predictable way are therefore of great interest. However, although the overall modular structure of NRPSs suggests the possibility of adjusting domain specificity and selectivity, only a few examples have been reported and these usually show a severe drop in production titre. Here we report a new strategy for the modification of NRPSs that uses defined exchange units (XUs) and not modules as functional units. XUs are fused at specific positions that connect the condensation and adenylation domains and respect the original specificity of the downstream module to enable the production of the desired peptides. We also present the use of internal condensation domains as an alternative to other peptide-chain-releasing domains for the production of cyclic peptides.
The donor acceptor substituted polyene 5-(4-dihexadecylaminophenyl)-2-methyl-2,4-pentadienal (DHAP) is--due to its amphiphilic nature--a promising candidate for the Langmuir-Blodgett (LB) technique. The molecule was studied as a monolayer on a pure water surface under argon atmosphere. Monolayers and multilayers were transferred onto solid support. The films showed a high degree of order in the monolayer as well as in thick multilayers. LB films were investigated with polarisation dependent UV/VIS absorption spectroscopy. The film spectra showed additional absorption peaks which were not present in the spectra of the molecules in solution. The relative peak intensities were highly dependent on the orientation of the electric field vector with respect to the substrate normal. To get a detailed picture of the arrangement of the films on the molecular level, we studied the polarisation dependence of the FTIR spectra in different experimental set-ups. The spectra showed a perpendicular orientation of the conjugated system with respect to the substrate, whereas the backbone of the saturated hydrocarbon chains showed a medium tilt angle of 20.0 ° with respect to the substrate normal. X-ray small angle diffraction measurements were applied to investigate the thickness of the LB layers. From the position of the Bragg peaks, a thickness of 5.45 nm per bilayer can be calculated, in agreement with a bilayer model showing different molecular alignment of the molecules transferred during upstroke and downstroke.
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