Synthesis of bombyxin-IV, an insulin superfamily peptide from the silkworm, Bombyx mori, by stepwise and selective formation of three disulfide bridges.
We report the synthesis of bombyxin-IV, a disulfide-linked, heterodimeric, insulin superfamily peptide from the silkworm, Bombyx mori. The two chains (A- and B-chains) were synthesized separately by the solid-phase method using fluoren-9-ylmethoxycarbonyl (Fmoc) group as a protecting group for alpha-amino group. Three disulfide bonds were bridged step by step (A6-A11, A20-B22, and A7-B10) in a good yield. Synthetic bombyxin-IV was identical with natural one with regard to the retention time on a reversed-phase column and the molecular weight measured by mass spectrometry. Circular dichroism (CD) spectrum of the synthetic bombyxin-IV was very similar to that of the natural one. The specific activity of synthetic bombyxin-IV is equal to that of natural one (0.1 ng/Samia unit). These results suggest that the synthetic bombyxin-IV has the tertiary structure identical with the natural peptide. Our method developed for synthesis of bombyxin-IV would be generally applicable to the synthesis of insulin-like heterodimeric peptides.
Maruyama
K
K
Department of Agricultural Chemistry, Faculty of Agriculture, University of Tokyo, Japan.
Nagata
K
K
Tanaka
M
M
Nagasawa
H
H
Isogai
A
A
Ishizaki
H
H
Suzuki
A
A
D000595:Amino Acid Sequence; D000818:Animals; D012831:Bombyx; D002851:Chromatography, High Pressure Liquid; D004220:Disulfides / Q000138:chemical synthesis*; D007301:Insect Hormones / Q000138:chemical synthesis* / Q000737:chemistry; D019476:Insect Proteins; D046911:Macromolecular Substances; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000138:chemical synthesis* / Q000737:chemistry; D014364:Tryptophan / Q000737:chemistry
D004220:Disulfides; D007301:Insect Hormones; D019476:Insect Proteins; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; C064115:bombyxin IV protein, Bombyx mori; D014364:Tryptophan