The first total synthesis of the peptaibol hypomurocin A1 and its conformation analysis: an application of the 'azirine/oxazolone method'.
The first total synthesis of Hypomurocin A1 (HM A1) in solution phase is described. As members of the peptaibol family, hypomurocins are constituted by two groups of peptides: six undecapeptides (undecamers) in the HM A group and six octadecapeptides (18-mers) in the HM B group. The synthesis presented has been successfully achieved by the 'azirine/oxazolone method' to introduce the two Aib-Pro sequences included in this undecapeptaibol in one step with methyl 2,2-dimethyl-2H-azirine-3-prolinate as the building block. The coupling reactions of the Z-protected amino acids or peptide acids involved the use of N,N,N',N'-tetramethyluronium tetrafluoroborate (TBTU) and 1-hydroxybenzotriazole (HOBt), and led to the peptides in good-to-very-good yields. The peptides were purified by reverse-phase HPLC and characterized by NMR spectroscopy (1H, 13C, COSY, TOCSY, HSQC, HMBC, ROESY), ESI-MS, IR, elemental analysis, optical rotation, and X-ray crystallography. An NMR analysis of HM A1 was also carried out in deuterated micelles to perform a structural comparison of the helix in solution and in membranes.
Pradeille
Nicolas
N
Organisch-chemisches Institut der Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich.
Zerbe
Oliver
O
Möhle
Kerstin
K
Linden
Anthony
A
Heimgartner
Heinz
H
D000595:Amino Acid Sequence; D005656:Fungal Proteins / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry*; D054848:Peptaibols; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation
D005656:Fungal Proteins; D009842:Oligopeptides; D054848:Peptaibols; D010455:Peptides; C517378:hypomurocin A1