186132-96-7Relevant articles and documents
Modular Chemoenzymatic Synthesis of GE81112 B1 and Related Analogues Enables Elucidation of Its Key Pharmacophores
Zwick, Christian R.,Sosa, Max B.,Renata, Hans
, p. 1673 - 1679 (2021/01/25)
The GE81112 complex has garnered much interest due to its broad antimicrobial properties and unique ability to inhibit bacterial translation initiation. Herein we report the use of a chemoenzymatic strategy to complete the first total synthesis of GE81112 B1. By pairing iron and α-ketoglutarate dependent hydroxylases found in GE81112 biosynthesis with traditional synthetic methodology, we were able to access the natural product in 11 steps (longest linear sequence). Following this strategy, 10 GE81112 B1 analogues were synthesized, allowing for identification of its key pharmacophores. A key feature of our medicinal chemistry effort is the incorporation of additional biocatalytic hydroxylations in modular analogue synthesis to rapidly enable exploration of relevant chemical space.
Propargyloxyproline Regio- and Stereoisomers for Click-Conjugation of Peptides: Synthesis and Application in Linear and Cyclic Peptides
Northfield, Susan E.,Mountford, Simon J.,Wielens, Jerome,Liu, Mengjie,Zhang, Lei,Herzog, Herbert,Holliday, Nicholas D.,Scanlon, Martin J.,Parker, Michael W.,Chalmers, David K.,Thompson, Philip E.
, p. 1365 - 1372 (2015/09/15)
The use of the click reaction for the introduction of conjugate groups, such as affinity or fluorescent labels, to a peptide for the study of peptide biochemistry and pharmacology is widespread. However, the nature and location of substituted 1,2,3-triazoles in peptide sequences may markedly affect conformation or binding as compared with native sequences. We have examined the preparation and application of propargyloxyproline (Pop) residues as a precursor to such peptide conjugates. Pop residues are available in a range of regio- and stereoisomers from hydroxyproline precursors and are readily prepared in Fmoc-protected form. They can be incorporated routinely in peptide synthesis and broadly retain the conformational properties of the parent proline containing peptides. This is exemplified by the preparation of biotin- and fluorophore-labelled peptides derived from linear and cyclic peptides.
3S-Fluoroproline as a probe to monitor proline isomerization during protein folding by 19F-NMR
Thomas, Colin A.,Talaty, Erach R.,Bann, James G.
supporting information; experimental part, p. 3366 - 3368 (2009/12/26)
Variable-temperature inversion transfer NMR is used to determine the kinetic and thermodynamic parameters of cis-trans isomerization of N-Ac-(3R) and (3S)-fluoroproline-OMe.
