The University of Southampton
University of Southampton Institutional Repository

Solid phase synthesis and applications of sulfur bridged peptides

Solid phase synthesis and applications of sulfur bridged peptides
Solid phase synthesis and applications of sulfur bridged peptides

This thesis describes the development of methodologies for the first total solid phase biomimetic synthesis of an analogue of the ring B of nisin, a polycyclic peptide antibiotic. As part of this research project a new method for the chemoselective oxidation of sulfides to sulfoxides was developed and shown to be a mild, neutral and efficient tool to access peptidic and non-peptidic sulfoxides, both in solution and on the solid phase. Due to its chemoselectivity the method enabled the solid phase synthesis of a methyl cysteine peptide sulfoxide in the presence of a trityl protected cysteine residue which, following synthetic elaborations on resin, allowed the preparation of a dehydro thiol peptide, precursor of ring B of nisin. This cyclised to give the lanthionine derivative as a single diastereoisomer. Preliminary studies were also carried out towards the synthesis of an analogue of the DE ring of nisin.

In addition, an efficient and rapid solid phase route to cysteine derivatives was developed and applied to the synthesis of a library of one of the most potent classes of organogelators discovered to date. The crude peptides were successfully screened and a subclass, the p-halogen benzoyl derivatives, showed outstanding gelating properties. In particular, a new 'super gelator' was identified. The p-fluoro analogue was able to gelatinise DMSO/water mixtures at the remarkably low concentration of 1.3 mM.

University of Southampton
Matteucci, Mizio
3c1b1bfd-2c90-41f2-8f9e-a491e3427c61
Matteucci, Mizio
3c1b1bfd-2c90-41f2-8f9e-a491e3427c61

Matteucci, Mizio (2003) Solid phase synthesis and applications of sulfur bridged peptides. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

This thesis describes the development of methodologies for the first total solid phase biomimetic synthesis of an analogue of the ring B of nisin, a polycyclic peptide antibiotic. As part of this research project a new method for the chemoselective oxidation of sulfides to sulfoxides was developed and shown to be a mild, neutral and efficient tool to access peptidic and non-peptidic sulfoxides, both in solution and on the solid phase. Due to its chemoselectivity the method enabled the solid phase synthesis of a methyl cysteine peptide sulfoxide in the presence of a trityl protected cysteine residue which, following synthetic elaborations on resin, allowed the preparation of a dehydro thiol peptide, precursor of ring B of nisin. This cyclised to give the lanthionine derivative as a single diastereoisomer. Preliminary studies were also carried out towards the synthesis of an analogue of the DE ring of nisin.

In addition, an efficient and rapid solid phase route to cysteine derivatives was developed and applied to the synthesis of a library of one of the most potent classes of organogelators discovered to date. The crude peptides were successfully screened and a subclass, the p-halogen benzoyl derivatives, showed outstanding gelating properties. In particular, a new 'super gelator' was identified. The p-fluoro analogue was able to gelatinise DMSO/water mixtures at the remarkably low concentration of 1.3 mM.

Text
906209.pdf - Version of Record
Available under License University of Southampton Thesis Licence.
Download (16MB)

More information

Published date: 2003

Identifiers

Local EPrints ID: 465039
URI: http://eprints.soton.ac.uk/id/eprint/465039
PURE UUID: 078eaacd-64a5-4335-8fb3-1e0c49d00388

Catalogue record

Date deposited: 05 Jul 2022 00:18
Last modified: 16 Mar 2024 19:54

Export record

Contributors

Author: Mizio Matteucci

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×