Solid-phase synthesis of cyclic peptide chitinase inhibitors: SAR of the argifin scaffold
Dixon, M.J., Nathubhai, Amit, Andersen, O.A., van Aalten, D.M.F. and Eggleston, I.M. (2008) Solid-phase synthesis of cyclic peptide chitinase inhibitors: SAR of the argifin scaffold. Organic & Biomolecular Chemistry, 7. pp. 259-268. ISSN 1477-0520
Item Type: | Article |
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Abstract
A new, highly efficient, all-solid-phase synthesis of argifin, a natural product cyclic pentapeptide
chitinase inhibitor, is reported. The synthesis features attachment of an orthogonally protected Asp
residue to the solid support and assembly of the linear peptide chain by Fmoc SPPS prior to cyclisation
and side-chain manipulation on-resin. Introduction of the key N-methyl carbamoyl-substituted Arg
side chain is achieved via derivatisation of a selectively protected Orn residue, prior to cleavage from the
resin and side-chain deprotection. A severe aspartimide side-reaction observed upon final deprotection
is circumvented by the use of a novel aqueous acidolysis procedure. The flexibility of the synthesis is
demonstrated by the preparation of a series of argifin analogues designed from the X-ray structure of
the natural product in complex with a representative family 18 chitinase.
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More Information
Depositing User: Amit Nathubhai |
Identifiers
Item ID: 9794 |
Identification Number: https://doi.org/10.1039/b815077j |
ISSN: 1477-0520 |
URI: http://sure.sunderland.ac.uk/id/eprint/9794 | Official URL: http://pubs.rsc.org/en/content/articlelanding/2009... |
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Catalogue record
Date Deposited: 10 Aug 2018 12:38 |
Last Modified: 18 Dec 2019 16:07 |
Author: | M.J. Dixon |
Author: | Amit Nathubhai |
Author: | O.A. Andersen |
Author: | D.M.F. van Aalten |
Author: | I.M. Eggleston |
University Divisions
Faculty of Health Sciences and WellbeingFaculty of Health Sciences and Wellbeing > School of Pharmacy and Pharmaceutical Sciences
Subjects
Sciences > ChemistryActions (login required)
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