Total synthesis of
[Glu40Gly]CP10 by native chemical ligation. (A)
Analytical RP-HPLC of the synthetic peptide fragments
[Glu40Gly]CP10(1–40)-αCOSR and CP10(41–88)
dissolved at 6 mg/ml in 0.1 M Tris⋅HCl buffer (pH 8.2)
containing 6 M guanidine⋅HCl at t = 0.
(Center and Right) Electrospray mass
spectra show the m/z ratios of the
[Glu40Gly]CP10(1–40)-αCOSR peptide (3rd to 5th ionized
states) with an observed molecular mass of 4749.8 ± 0.5 Da (calc.
4750.2 Da, average isotope composition), and the CP10(41–88) peptide
(2nd to 5th ionized states) with an observed molecular mass of
5518.6 ± 0.9 Da (calc. 5518.2 Da, average isotope composition).
(B) LC-MS analysis of the ligation reaction after
t = 3 h. Peaks A, B, and C represent unreacted
[Glu40Gly]CP10(1–40)-αCOSR,
[Glu40Gly]CP10(1–40) as the free C-terminal acid, and
[Glu40Gly]CP10(1–40)-αCOS-C6H5,
respectively. Peaks D and F had a mass indicating the presence of
CP10(1–88) esterified through the Cys-41 by CP10(1–40) (14,665 Da),
and the CP10(1–88)[Cys-41-thiophenol] mixed disulfide (10,199 Da),
respectively. ES-MS of purified [Glu40Gly]CP10 (6th to 12th ionized
states), peak E, had an observed molecular mass of 10,091.4 ± 1.1
Da; (calc. 10,091.3 Da, average isotope composition).