High helicities of Lys-containing, Ala-rich peptides are primarily attributable to a large, context-dependent Lys stabilization

Peptides 1K, YKGGGAAAAAAAAKAAAAAAGGGK-NH₂; 2K, YKGGGAAAAAKAAAAAKAAAAAAGGGK-NH₂; and 3K, YKGGGAAAAKAAAAKAAAAKAAAGGGK-NH₂ have been prepared by solid-phase synthesis, purified, and characterized by amino acid analysis, MALDI mass spectrometry, and ultracentrifugation. Their circular dichroism (CD) spectra of unaggregated solutions are reported for measurements in 0.01 M NaCl at 2, 25, and 60°C and at 2 °C in aqueous guanidinium hydrochloride (0-3 M) and aqueous trifluoroethanol (TFE, 0-15 mol %). The CD spectra exhibit a helical signature in 0.01 M NaCl or in water- TFE at 2 °C, and the intensities of the mean residue ellipticities at the minimums of 222 nm in 0.01 M NaCl are (1K) -9100, (2K) -18 100, and (3K) -19 900 deg cm^-1 dmol^-1. These ellipticities are accurately modeled using a Lifson-Roig algorithm by the helical propensities previously reported by Renold et al. (Renold, P.; Tsang, K.-Y.; Shimizu; L. S.; Kemp, D. S. J. Am. Chem. Soc. 1996, 118, 12234-12235.) but not by those of Doig and Baldwin (Doig, A. J.; Baldwin, R. L. Protein Sci. 1995, 4, 13257-1336.). The helicities of peptides such as 1K, 2K, and 3K are best attributed tO a lysine stabilization and not to an intrinsic helix propensity of alanine.