NMR analysis of AzK-KIIIA,
S-m3-HwTx-IV, and [m3-HwTx-IV]-[PEG80]-[K-KIIIA].
(A) Secondary Hα chemical
shifts of μ-KIIIA29 and AzK-KIIIA
obtained from sequence-specific resonance assignments using two-dimensional
TOCSY and NOESY spectra. The secondary Hα shifts aligned throughout
Asn3–Cys17. The N-terminal modification with AzK had chemical
shift differences of 0.37 ppm for Cys1 Hα and 0.12 ppm for Cys2
Hα. The x-axis shows the sequence of AzK-KIIIA.
The hash (#) indicates AzK, and the asterisk (*) indicates C-terminal
amidation. (B) 1H NMR spectra [600 MHz, 25 °C, 90/10%
(v/v) H2O/D2O] of AzK-KIIIA, S-m3-HwTx-IV, and [m3-HwTx-IV]-[PEG80]-[K-KIIIA]. The spectrum
of [m3-HwTx-IV]-[PEG80]-[K-KIIIA] was the sum of the spectra
of its individual peptide components as is exemplified for the tryptophan
ε-NH region of AzK-KIIIA (magenta dots) and S-m3-HwTx-IV
(green dots). Additional signals in the fingerprint region of the
conjugate correspond to five secondary amide protons present in the
synthetic PEG80 linker, and the C5 proton in the 1,2,3-triazole occurring
in the bivalent compound.