Partner und Internationale Organisationen
(Englisch)
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A, B, HR, CZ, DK, FIN, F, D, GR, H, IRL, I, NL, PL, P, RO, SI, E, S, CH, GB
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Abstract
(Englisch)
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The last phase of the COST project has brought some surprising results, that actually appear to be more important than we had foreseen. This has to do with the notion of homochirality of the synthesized polypeptide chains. In particular: in the work dealing with the liposome-assisted polycondensation of NCA (N-carboxyanhydride)-amino acids it has been shown that racemic NCA-Trp condensation affords chains with preferential homochiral sequences: the homochiral blocks become increasingly over-represented with increasing oligomer length if compared with the statistically (Bernoullian) distributions. Based on these first observation, we have also tackled other three questions related to this stereoselective NCA-Trp-condensation. The first question concerns the kinetic mechanism that is responsible for the over-representation of homochiral sequences in the presence as well as in the absence of liposomes. To this aim, we have investigated whether and to what extent the selection of the entering chiral monomer-unit is governed by the chirality of the penultimate residue. This analysis allows one to suggest that the polycondensation corresponds to a second or higher order Markov process. The second question considered in our work is whether the preferential formation of homochiral sequences, originally found in NCA-Trp-amino acid condensations, is observed also for amino acids other than Trp as well as for mixtures of different amino acids. To clarify this point, we have analyzed by liquid chromatography mass spectrometry (LC-MS) the condensation products of racemic NCA-D-Leu/perdeuterated NCA-L-Leu and racemic NCA-D-Ile/perdeuterated NCA-L-Ile in an aqueous solution without liposomes. This analysis permits us to show that the preferential homochiral growth occurs also with Leu and Ile. By LC-MS analysis we could show that under the same conditions also mixtures of equal amounts of the L-and D-forms of different amino acids, such as Trp/Leu, Leu/Ile and Trp/Leu/Ile exhibit similar behavior. The third question we have considered in our work is related to the effect of liposomes on the NCA-Trp condensation, namely whether the chemical structure of the lipid in the liposomes and consequently their physical state has an influence on the stereoselectivity of the NCA-Trp condensation. To this aim, experiments are carried out at different temperatures in the presence of DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphorylcholine) liposomes, below as well as above the liquid-analogue/crystalline-analogue transition temperature. The answer to the third question is that basically the same results are obtained independently on the physical state of the lipid.
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