MRC National Institute for Medical Research, London
Science for Health
John Offer group
Acyl transfer for chemical biology and synthesis
Post translationally-modified proteins can now be synthesised with a combination of ligation and optimised peptide synthesis, giving atom by atom control over the product. Chemical ligation can be combined with biological expression systems, enabling the semi-synthesis of proteins containing non-natural amino acids with a broad range of applications. The focus of this laboratory is to use emerging ligation techniques to build biological macromolecules. However, the generality of chemical ligation is limited to a handful of favorable ligation sites, and so in our lab novel auxiliary approaches have been developed to universalise it. We are aso applying chemical ligation to the synthesis of chemically defined peptide-oligosaccharide glycoconjugates as HIV vaccines.
Auxiliary–assisted ligation chemistry can chemoselectively join a wide range of peptides together without needing elaborate protecting group strategies. We are applying it to the synthesis of small cyclic peptides, attractive lead compounds for screening and the development of orally available therapeutics.
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Chemical ligation methods for the synthesis of proteins and post-translationally modified proteins
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Single amino acid incorporation using orthogonal ligation
Selected publications
- Burlina, F; Dixson, DD; Doyle, RP; Chassaing, G; Boddy, CN; Dawson, P and Offer, J (2008)
Orthogonal ligation: a three piece assembly of a PNA-peptide-PNA conjugate.
Chemical Communications , 2785-2787 PubMed abstract - Scanlan, CN; Offer, J; Zitzmann, N and Dwek, RA (2007)
Exploiting the defensive sugars of HIV-1 for drug and vaccine design.
Nature 446, 1038-1045 PubMed abstract
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