title: Enzymatic transhalogenation of dendritic RGD peptide constructs with the fluorinase.
abstract: The substrate scope of fluorinase enzyme mediated transhalogenation reactions is extended. Substrate tolerance allows a peptide cargo to be tethered to a 5'-chloro-5'-deoxynucleoside substrate for transhalogenation by the enzyme to a 5'-fluoro-5'-deoxynucleoside. The reaction is successfully extended from that previously reported for a monomeric cyclic peptide (cRGD) to cargoes of dendritic scaffolds carrying two and four cyclic peptide motifs. The RGD peptide sequence is known to bind upregulated αVβ3 integrin motifs on the surface of cancer cells and it is demonstrated that the fluorinated products have a higher affinity to αVβ3 integrin than their monomeric counterparts. Extending the strategy to radiolabelling of the peptide cargoes by tagging the peptides with [(18)F]fluoride was only moderately successful due to the poor water solubility of these higher order peptide scaffolds although the strategy holds promise for peptide constructs with improved solubility.
authors.affiliation: School of Chemistry and Biomedical Sciences Research Centre, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK. do1@st-andrews.ac.uk.
authors.forename: Stephen
authors.initials: S
authors.lastname: Thompson
authors.forename: Ian N
authors.initials: IN
authors.lastname: Fleming
authors.forename: David
authors.initials: D
authors.lastname: O'Hagan
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D003853:Deoxyribonucleosides / Q000737:chemistry* / Q000378:metabolism*; D003855:Deoxyribose / Q000031:analogs & derivatives / Q000378:metabolism; D054879:Halogenation; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008958:Models, Molecular; D010088:Oxidoreductases / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000378:metabolism*; D013302:Streptomyces / Q000201:enzymology*
chemical_list: D001426:Bacterial Proteins; D003853:Deoxyribonucleosides; D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic; C507169:cyclic arginine-glycine-aspartic acid peptide; D003855:Deoxyribose; D010088:Oxidoreductases; C495766:fluorinase