Design of general tags to incorporate iodine atoms into peptides for radio-contrast imaging.
Di-Iodotyrosinated Peptide Imaging of Cartilage (DIPIC) is being patented by our group as a method for the visualisation of articular cartilage in computed tomography (CT) scans (1). DIPIC is an evolution on the WYRGRL peptide, panned from a phage display library to bind to cartilage through collagen type-II (2) with a novel method of incorporation of iodine atoms, required for radio-contrast, using 3,5-di-iodotyrosine (DIT) residues. We have successfully defined several lead DIPIC sequences with up to two DIT residues, but are faced with solubility issues when trying to incorporate more DITs. To make this method of iodine incorporation generally applicable to other peptides, we are proposing to design several generic tags (in the same vein as a FLAG or HA tag) to maximise DIT incorporation and solubility. The student will explore the designs of tags for peptides in solution and peptides that would form hydrogels.
Techniques you will learn:
Peptide Synthesis, Circular Dichroism, NMR Solution Structure, Peptide Hydrogels.
Day to day supervisor:
Ngee Han Lim, The Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS) (firstname.lastname@example.org) - https://www.kennedy.ox.ac.uk/research/molecular-imaging-group
Chemistry Co-supervisor: Prof. Tim Claridge
- Fowkes MM, Das Neves Borges P, Brennan PE, Vincent TL, Lim NH. Development of Targeted Radioopaque Peptide Contrast Agents. Manuscript in preparation.
- Rothenfluh DA, Bermudez H, O’Neil CP, Hubbell JA. Biofunctional polymer nanoparticles for intra-articular targeting and retention in cartilage. Nature Materials 2008 248-254
- Hu HY, Lim NH, Juretscheke H, Ding-Pfennigdroff D, Florian P, Kohlmann M, Kandira A, Peter von Kries J, Sass J, Rudolphi KA, Wendt KU, Nagase H, Plettenburg O, Nazare M, Schultz C. Chemical Science 2015 6,6256-6261. In vivo visualization of osteoarthritic hypertrophic lesions.