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Synthesis of β 3 ‐Peptides and Mixed α / β 3 ‐Peptides by Thioligation
Author(s) -
Kimmerlin Thierry,
Seebach Dieter,
Hilvert Donald
Publication year - 2002
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 - 10.1002/1522-2675(200206)85:6<1812::aid-hlca1812>3.0.co;2-e
Subject(s) - chemistry , peptide , high performance liquid chromatography , cysteine , mass spectrometry , peptide synthesis , circular dichroism , solid phase synthesis , aqueous solution , chromatography , native chemical ligation , stereochemistry , organic chemistry , biochemistry , enzyme
Five β ‐peptide thioesters ( 1 – 5 , containing 3, 4, 10 residues) were prepared by manual solid‐phase synthesis and purified by reverse‐phase preparative HPLC. A β ‐undecapeptide ( 6 ) and an α ‐undecapeptide ( 7 ) with N ‐terminal β 3 ‐HCys and Cys residues were prepared by manual and machine synthesis, respectively. Coupling of the thioesters with the cysteine derivatives in the presence of PhSH ( Scheme and Fig. 1 ) in aqueous solution occurred smoothly and quantitatively. Pentadeca‐ and heneicosapeptides ( 8 – 10 ) were isolated, after preparative RP‐HPLC purification, in yields of up to 60%. Thus, the so‐called native chemical ligation works well with β ‐peptides, producing larger β 3 ‐ and α / β 3 ‐mixed peptides. Compounds 1 – 10 were characterized by high‐resolution mass spectrometry (HR‐MS) and by CD spectroscopy, including temperature and concentration dependence. β ‐Peptide 9 with 21 residues shows an intense negative Cotton effect near 210 nm but no zero‐crossing above 190 nm, ( Figs. 2–4 ), which is characteristic of β ‐peptidic 3 14 ‐helical structures. Comparison of the CD spectra of the mixed α / β ‐pentadecapeptide ( 10 ) and a helical α ‐peptide ( Fig. 5 ) indicate the presence of an α ‐peptidic 3.6 13 helix.