The synthesis of peptides can be considered as the rate-limiting step in the development of peptide-based medicines. Synthetic methods currently available are limited by several aspects, including the high cost of production or excessive waste when applied to large-scale synthesis. The development of a new solution-phase synthesis of peptides is described herein. Initial studies focus on the synthesis of α-peptides in the C-terminal direction, though the occurrence of epimerisation during chain elongation shows the limitation of this approach. Attempts to reduce this problem and to gain a better insight into the epimerisation processes involved are described. The unsuccessful application of this initial strategy to the synthesis of β-peptides is also discussed. A new procedure involving the coupling of amino acids or peptide acids with slight excesses of pentafluorophenyl esters in a THF/water solvent mixture in the N-terminal direction is developed and discussed. Contrary to modern repetitive solution-phase peptide synthesis procedures, this approach does not require time-consuming neutralisation reactions and reduces significantly the number of operation units that are necessary to obtain peptide intermediates. The efficiency of the new method is demonstrated by the rapid synthesis of short hydrophobic and hydrophilic peptides, the antimalarial cyclopeptide mahafacyclin B and a protected form of the hydrophilic pentapeptide Gly-Arg-Gly-Asp-Ser. Binding studies of the complex between 1-(3-Dimethylaminopropyl)-3-ethylurea hydrochloride (EDU.HCl) and triethylammonium trifluoroacetate are described and the potential application of EDU.HCl as an artificial carboxylate receptor to increase the acidity of trifluoroacetic acid is discussed.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:540483 |
| Date | January 2010 |
| Creators | Carnapete Alves Meneses, Célia Clarisse |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=166204 |
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