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Reversible Folding of a β‐Hairpin Peptide by a Metal‐Chelating Amino Acid
Author(s) -
Reutzel Jan,
Diogo Timm M.,
Geyer Armin
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201700698
Subject(s) - chemistry , chelation , peptide , trimer , amino acid , metal , stereochemistry , hydrolysis , peptide sequence , phosphonate , combinatorial chemistry , organic chemistry , biochemistry , dimer , gene
5‐(1‐Hydroxy‐pyridin‐2(1 H )‐onyl)‐ l ‐alanine (Hop) is a N ‐hydroxy‐1,2‐pyridone functionalized α‐amino acid with the desired metal‐chelating properties of DOPA (3,4‐dihydroxy phenylalanine) but without its unwanted redox activity. The Fmoc‐protected amino acid Fmoc‐ l ‐Hop( t Bu)‐OH ( 11 ) was synthesized from glycine phosphonate followed by enzymatic hydrolysis of the methyl ester yielding the Hop l ‐isomer in 96 % ee . The amino acid 11 is used in automated peptide synthesis for the assembly of a 14mer β‐hairpin peptide with the sequence [dsb 1, 14 ]H‐CH X ETGKHGHKLVC‐OH (X=W, l ‐Hop). While the 10 π electron containing indole side chain of l ‐Trp in peptide 14 completes the formation of a hydrophobic cluster and results in 90 % folding, the folded fraction is significantly decreased to approximately 30 % for the 6 π electron l ‐Hop side chain in peptide 16 . Metal chelation of Ga 3+ reconstitutes the folding of 16 to above 60 % due to the formation of the Ga( 16 ) 3 trimer. The chelation process of 16 is monitored by NMR spectroscopy and the subsequent release of Ga 3+ by a competitive metal chelator exemplifies the reversible oligomerization of peptide epitopes by metal chelation, bearing the opportunity to synthesize protein‐sized aggregates on the basis of reversible chemistry in water.