The synthesis of a series of peptides from the processing region of interleukin-1-β precursor (IL-1-β-pre) has been carried out using automated solid-phase methods. The subpeptide comprising residues 102-138 was found to possess inhibitory activity towards the cleavage of IL-1-β-pre in studies using human monocyte cell lines. Attempts have been made to define more closely the region of the peptide responsible for this activity. Overlapping dodecapeptides have been prepared which cover this region of the precursor. The highest level of residual biological activity was found to reside in the subpeptide 111-122, comprising six residues on either side of the site of processing. Various derivatives of this peptide have been prepared in order to enhance this activity. Several of these peptides have been investigated by high-field nuclear magnetic resonance (NMR). Computer assignment of the spectra of most of the dodecapeptides has been achieved. The NMR spectra of an analogue of IL-1-β-pre 102-138 where cysteine-124 has been replaced by alanine (Ala-124-IL-1-β-pre 102-138) have been obtained and partially assigned. Analysis of through-space interactions indicated that these peptides adopt random conformations. A survey of protecting groups for the side-chain amide functional groups of asparagine and glutamine in solid-phase peptide synthesis has been carried out. Novel dibenzosuberenyl-type derivatives have been prepared and successfully applied to the preparation of a series of peptides. A comparison between these derivatives and commonly used alternatives (unprotected amide, trityl and 4,4'dimethoxybenzhydryl) indicated that the trityl group was the most generally suitable means of incorporating these amino acids.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:654373 |
| Date | January 1991 |
| Creators | Maclean, Derek |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/15249 |
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