Perfluoroheteroaromatics as Tools for Peptide Modification

The use of peptides as drugs has been hampered due to, in part, poor stability in vivo. To address this issue, heteroaromatics have been investigated in an attempt to improve enzymatic stability. In particular, pentafluoropyridine has emerged as an interesting tool for peptide modification due to its reactivity towards nucleophilic peptide side chains. Small dipeptides were synthesised, tagged using pentafluoropyridine and further functionalised using thiophenolate resulting in a surprising substitution pattern. Bioactive peptides Oxytocin, Vasopressin and GLP-1 were also synthesised and reacted with pentafluoropyrydine using selective and non-selective "tagging" techniques.The stability of these modified peptides were tested and compared to native peptides to establish the validity of using pentafluoropyridine as a tool to improve peptide stability.