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Design and Synthesis of a Monofluoro‐Substituted Aromatic Amino Acid as a Conformationally Restricted 19 F NMR Label for Membrane‐Bound Peptides
Author(s) -
Tkachenko Anton N.,
Mykhailiuk Pavel K.,
Radchenko Dmytro S.,
Babii Oleg,
Afonin Sergii,
Ulrich Anne S.,
Komarov Igor V.
Publication year - 2014
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201301737
Subject(s) - chemistry , peptide , gramicidin s , stereochemistry , gramicidin , amino acid , circular dichroism , residue (chemistry) , peptide synthesis , solid phase synthesis , helix (gastropod) , phenylalanine , nuclear magnetic resonance spectroscopy , aromatic amino acids , membrane , organic chemistry , biochemistry , ecology , snail , biology
A monofluoro‐substituted amino acid was designed to serve as a conformationally restricted label for solid‐state 19 F 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 Cα‐tetrasubstituted amino acid cannot racemize, it showed full compatibility with solid‐phase peptide synthesis protocols. According to circular dichroism analysis and molecular modeling, the 19 F‐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 β‐turn nor in an α‐helix.