The design of a solid phase peptide synthesis linker, which on cleavage with trifluoroacetic acid leaves the peptide C-terminus with a hydroxy ester functionality, is described herein. The enhanced rate of hydrolysis of hydroxy esters and carbamates under basic conditions has been investigated with a view to utilising this effect in the orthogonal protection of amino acid side chains during the syntheses of large peptides. The development of protecting groups for both acid and amine side chains has been investigated in order that the syntheses of proteins via chemical fragment coupling can proceed with a high degree of fidelity. The base hydrolysis of various esters and carbamates has been studied, as has the stability of these compounds to acidic conditions. The syntheses of a number of protecting group candidates based on tris(hydroxymethyl) derivatives has been undertaken and conditions for their removal optimised. The syntheses of various test compounds and small peptides utilising these types of protecting groups has been completed. The synthesis, purification and deprotection of a 32 residue peptide, with one lysine protected as the tris(hydroxymethyl)nitromethyl carbamate is also reported. The synthesis of a section of the CD4 binding region of the HIV coat protein Gp120 has been investigated. Various methods of cysteine protection have been studied and the difficulties associated with solubility and protecting group removal highlighted.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:643371 |
| Date | January 1996 |
| Creators | Comer, Alexander Robert John |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/14688 |
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