• Login
    View Item 
    •   DORA Home
    • Faculty of Health and Life Sciences
    • Leicester School of Pharmacy
    • View Item
    •   DORA Home
    • Faculty of Health and Life Sciences
    • Leicester School of Pharmacy
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Racemisation of N-Fmoc phenylglycine under mild microwave-SPPS and conventional stepwise SPPS conditions: attempts to develop strategies for overcoming this

    Thumbnail
    Date
    2012-03-26
    Author
    Elsawy, M.;
    Hewage, C.;
    Walker, B.
    Metadata
    Show attachments and full item record
    Abstract
    We have been engaged in the microwave-solid phase peptide synthesis (SPPS) synthesis of the phenylglycine (Phg)-containing pentapeptide H-Ala-Val-Pro-Phg-Tyr-NH2 (1) previously demonstrated to bind to the so-called BIR3 domain of the anti-apoptotic protein XIAP. Analysis of the target peptide by a combination of RP-HPLC, ESI-MS, and NMR revealed the presence of two diastereoisomers arising out of the racemisation of the Phg residue, with the percentage of the LLLDL component assessed as 49%. We performed the synthesis of peptide (1) using different microwave and conventional stepwise SPPS conditions in attempts to reduce the level of racemisation of the Phg residue and to determine at which part of the synthetic cycle the epimerization had occurred. We determined that racemisation occurred mainly during the Fmoc-group removal and, to a much lesser extent, during activation/coupling of the Fmoc-Phg-OH residue. Wewere able to obtain the desired peptide with a 71%diastereomeric purity (29%LLLDL as impurity) by utilizing microwave-assisted SPPS at 50 C and power 22Watts,when the triazine-derived coupling reagent DMTMM-BF4 was used, together with NMM as an activator base, for the incorporation of this residue and 20% piperidine as an Fmoc-deprotection base. In contrast, the phenylalanine analogue of the above peptide, H-Ala-Val-Pro-Phe-Tyr- NH2 (2), was always obtained as a single diastereoisomer by using a range of standard coupling and deprotection conditions. Our findings suggest that the racemisation of Fmoc-Phg-OH, under both microwave-SPPS and stepwise conventional SPPS syntheses conditions, is very facile but can be limited through the use of the above stated conditions.
    Description
    The Publisher's final version can be found by following the DOI link.
    Citation : Elsawy, M., Hewage, C., Walker, B. (2012) Racemisation of N-Fmoc phenylglycine under mild microwave-SPPS and conventional stepwise SPPS conditions: attempts to develop strategies for overcoming this. Journal of Peptide Science, 18(5), pp. 302-311.
    URI
    https://dora.dmu.ac.uk/handle/2086/19086
    DOI
    https://doi.org/10.1002/psc.2398
    Research Institute : Leicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)
    Peer Reviewed : Yes
    Collections
    • Leicester School of Pharmacy [1213]

    Submission Guide | Reporting Guide | Reporting Tool | DMU Open Access Libguide | Take Down Policy | Connect with DORA
    DMU LIbrary
     

     

    Browse

    All of DORACommunities & CollectionsAuthorsTitlesSubjects/KeywordsResearch InstituteBy Publication DateBy Submission DateThis CollectionAuthorsTitlesSubjects/KeywordsResearch InstituteBy Publication DateBy Submission Date

    My Account

    Login

    Submission Guide | Reporting Guide | Reporting Tool | DMU Open Access Libguide | Take Down Policy | Connect with DORA
    DMU LIbrary