Design and Synthesis of a Monofluoro-Substituted Aromatic Amino Acid as a Conformationally Restricted F-19 NMR Label for Membrane-Bound Peptides

作者：Tkachenko Anton N; Mykhailiuk Pavel K^*; Radchenko Dmytro S; Babii Oleg; Afonin Sergii; Ulrich Anne S; Komarov Igor V

来源：European Journal of Organic Chemistry, 2014, 2014(17): 3584-3591.

DOI：10.1002/ejoc.201301737

• Amino acids
• Proteins
• Membrane proteins
• Protein modifications
• Fluorine
• Solid-state NMR spectroscopy

A monofluoro-substituted amino acid was designed to serve as a conformationally restricted label for solid-state F-19 NMR distance measurements in membrane-bound peptides. The aromatic cis and trans isomers of 1-amino-3-(4-fluorophenyl)-cyclobutanecarboxylic acid were synthesized in five steps from diethyl 2-(4-fluorophenyl)propanedioate. They were incorporated into the antimicrobial peptide gramicidin S to replace a native D-phenylalanine residue. Because the C alpha-tetrasubstituted amino acid cannot racemize, it showed full compatibility with solid-phase peptide synthesis protocols. According to circular dichroism analysis and molecular modeling, the F-19-labeled analogues of the known helix-inducing amino acid (1-aminocyclobutane-1-carboxylic acid) do not disrupt the peptide conformation when substituted for Phe, neither in a beta-turn nor in an alpha-helix.

• 出版日期2014-6