Biosynthetic Incorporation of Fluorinated Amino Acids into Peptides and Proteins

Abstract

Native and engineered protein biosynthetic machinery processes a wide range of fluorinated a-amino acids for incorporation into peptides and proteins, either as substitutes for structurally similar amino acids normally found in proteins, or as additional ones. In the former case, replacement occurs wherever the normal amino acid is encoded, while the latter method is site-specific. The fluorinated peptides have a diverse variety of interesting properties. The biochemical synthetic methods are straightforward, to the point that they should routinely be assessed as alternatives to traditional solid-and solution-phase peptide synthesis.

Design, synthesis, and applications of ring‐functionalized histidines in peptide‐based medicinal chemistry and drug discovery

“…[136][137][138] Several biosynthetic methods have also been adopted for the synthesis or incorporation of amino acids in designed peptides. 139,140 A large number of literature reports confirm that ring-modified histidines are vital synthetic derivatives in search of bioactive and promising drug-like scaffolds. In search of ring-modified histidine containing bioactive scaffolds, a wide array of medicinally relevant novel structural genre of peptides have been reported with biological activity against microbes.…”

“…Thus, MW irradiation assisted protocols have been developed to rapidly access peptides in good yields 136–138 . Several biosynthetic methods have also been adopted for the synthesis or incorporation of amino acids in designed peptides 139,140 . A large number of literature reports confirm that ring‐modified histidines are vital synthetic derivatives in search of bioactive and promising drug‐like scaffolds.…”

Fluorine Chemistry

“…Blanch and Wentrup (University of Queensland) describe an investigation into fluorinated carbene reactive intermediates [1] ; Read and co-workers (UNSW) report on the synthesis of novel fluorous surfactant molecules [2] ; Chebib (University of Sydney) and co-workers describe the receptor binding properties of shape-controlled fluorinated GABA analogues [3] ; Matesic and co-workers (Australian Nuclear Science and Technology Organisation) publish a microfluidic protocol for the automated production of 18 F-labelled compounds [4] ; Fraser and Easton (ANU) review the state-of-the-art in biosynthesis approaches to fluorinated peptides and proteins [5] ; Gardiner (CSIRO) reviews the production and commercial applications of fluoropolymers [6] ; Patel and Liu (Macquarie University) describe the synthesis and conformational analysis of fluorinated N-heterocycles [7] ; Harper and co-workers (UNSW) report on the outcomes of S N 2 reactions performed in fluorinated ionic liquid media [8] ; Kassiou and co-workers (University of Sydney) report on the clandestine production of fluorinated recreational drugs [9] ; Hunter and co-workers (UNSW) describe an investigation of fluorinated proline derivatives as enantioselective organocatalysts [10] ; and in an international contribution to this issue, O'Hagan and co-workers (University of St Andrews, UK) report on the fluorovinyl thioether functional group as a novel potential bioisostere of thioester enolates. [11] I sincerely thank all of the authors who have made such fine contributions to this Research Front, as well as the editorial and administrative staff of Aust.…”