title: Relationship of sidechain hydrophobicity and alpha-helical propensity on the stability of the single-stranded amphipathic alpha-helix.
abstract: The aim of the present investigation is to determine the effect of alpha-helical propensity and sidechain hydrophobicity on the stability of amphipathic alpha-helices. Accordingly, a series of 18-residue amphipathic alpha-helical peptides has been synthesized as a model system where all 20 amino acid residues were substituted on the hydrophobic face of the amphipathic alpha-helix. In these experiments, all three parameters (sidechain hydrophobicity, alpha-helical propensity and helix stability) were measured on the same set of peptide analogues. For these peptide analogues that differ by only one amino acid residue, there was a 0.96 kcal/mole difference in alpha-helical propensity between the most (Ala) and the least (Gly) alpha-helical analogue, a 12.1-minute difference between the most (Phe) and the least (Asp) retentive analogue on the reversed-phase column, and a 32.3 degrees C difference in melting temperatures between the most (Leu) and the least (Asp) stable analogue. The results show that the hydrophobicity and alpha-helical propensity of an amino acid sidechain are not correlated with each other, but each contributes to the stability of the amphipathic alpha-helix. More importantly, the combined effects of alpha-helical propensity and sidechain hydrophobicity at a ratio of about 2:1 had optimal correlation with alpha-helix stability. These results suggest that both alpha-helical propensity and sidechain hydrophobicity should be taken into consideration in the design of alpha-helical proteins with the desired stability.
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, Canada.
authors.forename: O D
authors.initials: OD
authors.lastname: Monera
authors.forename: T J
authors.initials: TJ
authors.lastname: Sereda
authors.forename: N E
authors.initials: NE
authors.lastname: Zhou
authors.forename: C M
authors.initials: CM
authors.lastname: Kay
authors.forename: R S
authors.initials: RS
authors.lastname: Hodges
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D004355:Drug Stability; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D013696:Temperature; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D010455:Peptides