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 [18F]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.
Bibliographical noteWe thank EPSRC and the Scottish Imaging Network (SINAPSE) for grants. DO’H thanks the Royal Society for a Wolfson Research Merit Award and ST is grateful to the John and Kathleen Watson Scholarship for financial support. We are grateful to Dr Catherine Botting and Dr Sally Shirran of the St Andrews Mass Spectrometry Service for MALDI-MS acquisitions. We also thank Dr Sally Pimlott of the University of Glasgow for the use of radiochemistry facilities. Open access via RSC Gold for Gold.
- positon emission tomography
- RGD peptides