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Synthesis and CD Spectra of Fluoro‐ and Hydroxy‐Substituted β ‐Peptides
Author(s) -
Gessier François,
Noti Christian,
Rueping Magnus,
Seebach Dieter
Publication year - 2003
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200390150
Subject(s) - chemistry , heteroatom , peptide , stereochemistry , amino acid , nuclear magnetic resonance spectroscopy , alanine , nmr spectra database , hexa , valine , mass spectrum , protein secondary structure , mass spectrometry , crystallography , organic chemistry , ring (chemistry) , spectral line , biochemistry , physics , chromatography , astronomy
β ‐Amino acids 1 – 3 with OH and F substituents in the α ‐position have been prepared ( Scheme ) from the natural ( S )‐ α ‐amino acids alanine, valine, and leucine, and incorporated into β ‐hexa‐ and β ‐heptapeptides 4 – 12 . The peptide syntheses were performed according to a conventional solution strategy (Boc/Bn protection) with fragment coupling. The new β ‐peptides with (series a ) and without (series b ) terminal protection were isolated in HPLC‐pure form and characterized by NMR spectroscopy and MALDI mass spectrometry. The chemical properties as well as the patterns of the CD spectra ( Figs. 3–5 ) depend upon constitution (OH, F, F 2 substitution) and configuration ( l or u ) of the amino acid residues, upon the total number of OH and F substituents in the peptide chain, and upon the solvent used (H 2 O, MeOH, CF 3 CH 2 OH, (CF 3 ) 2 CHOH). No reliable clues regarding the structures can be obtained from these CD spectra. Only a full NMR analysis will be able to answer the questions: a ) with which known secondary structures ( Figs. 1 and 2 ) of β ‐peptides are the OH and F derivatives compatible? b ) Are new secondary structures enforced by the polar and/or H‐bonding backbone substituents? Furthermore, the β ‐peptides described here will enable us to study changes in chemical, enzymatic, and metabolic stability, and in physiological properties caused by the heteroatoms.