Enzymatic transhalogenation of dendritic RGD peptide constructs with the fluorinase

Stephen Thompson, Ian N. Fleming, David O’Hagan

Research output: Contribution to journalArticle

10 Citations (Scopus)
5 Downloads (Pure)

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 [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.
Original languageEnglish
Pages (from-to)3120-3129
Number of pages10
JournalOrganic & Biomolecular Chemistry
Volume14
Issue number11
Early online date15 Feb 2016
DOIs
Publication statusPublished - 21 Mar 2016

Fingerprint

peptides
Peptides
Cyclic Peptides
cargo
Scaffolds
Integrins
Solubility
Substrates
enzymes
Enzymes
Fluorides
solubility
Cells
fluorinase
arginyl-glycyl-aspartic acid
Water
marking
fluorides
affinity
cancer

Keywords

  • fluorinase
  • positon emission tomography
  • multimers
  • RGD peptides
  • radiolabelling

Cite this

Enzymatic transhalogenation of dendritic RGD peptide constructs with the fluorinase. / Thompson, Stephen; Fleming, Ian N.; O’Hagan, David.

In: Organic & Biomolecular Chemistry, Vol. 14, No. 11, 21.03.2016, p. 3120-3129.

Research output: Contribution to journalArticle

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