HIGH HELICITIES OF LYS-CONTAINING, ALA-RICH PEPTIDES ARE PRIMARILY ATTRIBUTABLE TO A LARGE, CONTEXT-DEPENDENT LYS STABILIZATION

Peptides 1K, YKGGGAAAAAAAAKAAAAAAAAAGGGK-NH2; 2K, YKGGGAAAAAKAAAAAKAAA AAAGGK-NH2; and 3K, YKGGGAAAAKAAAAKAAAAKAAAGGK-NH2 have been prepared by solid-phase synthesis, purified, and characterized by amino acid an alysis, MALDI mass spectrometry, and ultracentrifugation. Their circul ar dichroism (CD) spectra of unaggregated solutions are reported for m easurements in 0.01 M NaCl at 2, 25, and 60 degrees C and at 2 degrees C in aqueous guanidinium hydrochloride (0-3 M) and aqueous trifluoroe thanol (TFE, 0-15 mol %). The CD spectra exhibit a helical signature i n 0.01 M NaCl or in water-TFE at 2 degrees C, and the intensities of t he 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). T hese ellipticities are accurately modeled using a Lifson-Roig algorith m by the helical propensities previously reported by Renold et al. (Re nold, P.; Tsang, K.-Y.; Shimizu, L. S.; Kemp, D. S. J. Am. Chem. Sec. 1996, 118, 12234-12235.) but not by those of Doig and Baldwin (Doig, A . J.; Baldwin, R: L. Protein Sci. 1995, 4, 1325-1336.). The helicities of peptides such as 1K, 2K, and 3K are best attributed to a lysine st abilization and not to an intrinsic helix propensity of alanine.