NMR study of a 34‐residue N‐terminal fragment of the parathyroid‐hormone‐related protein secreted during humoral hypercalcemia of malignancy

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Abstract
The proton resonances of the biologically active peptide parathyroid-hormone-related protein (residues 1-34) were assigned using one-dimensional spin-decoupling techniques, two-dimensional correlated spectroscopy and by comparing the spectra of the peptides 1-20, 1-25, 1-29, 7-34 and 15-34. The conformation of 1-34 was determined using one- and two-dimensional nuclear Overhauser enhancement spectroscopy in the rotating frame. Amide proton temperature coefficients, vicinal coupling constants and circular dichoric spectra helped reveal a surprisingly compact structure with residues 3-9 forming .alpha.-helix, type-I .beta.-turns between residues 10-13 and 16-19 and several interactions between the N-terminal residues and the C-terminal residues. Of these latter, the strongest appeared to be between Asp-10 and Phe-22. One peptide surface in the deduced model presents multiple positive charges, while the opposite surface has a hydrophobic character possibly functioning to exclude water from the binding interface and enhancing the binding constant.

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