HELIX PROPENSITIES OF THE AMINO-ACIDS MEASURED IN ALANINE-BASED PEPTIDES WITHOUT HELIX-STABILIZING SIDE-CHAIN INTERACTIONS

Helix propensities of the amino acids have been measured in alanine-ba sed peptides in the absence of helix-stabilizing side-chain interactio ns. Fifty-eight peptides have been studied. A modified form of the Lif son-Roig theory for the helix-coil transition, which includes helix ca pping (Doig AJ, Chakrabartty A, Klingler TM, Baldwin RL, 1994, Biochem istry 33:3396-3403), was used to analyze the results. Substitutions we re made at various positions of homologous helical peptides. Helix-cap ping interactions were found to contribute to helix stability, even wh en the substitution site was not at the end of the peptide. Analysis o f our data with the original Lifson-Roig theory, which neglects cappin g effects, does not produce as good a fit to the experimental data as does analysis with the modified Lifson-Roig theory. At 0 degrees C, Al a is a strong helix former, Leu and Arg are helix-indifferent, and all other amino acids are helix breakers of varying severity. Because Ala has a small side chain that cannot interact significantly with other side chains, helix formation by Ala is stabilized predominantly by the backbone (''peptide H-bonds''). The implication for protein folding i s that formation of peptide H-bonds can largely offset the unfavorable entropy change caused by fixing the peptide backbone. The helix prope nsities of most amino acids oppose folding; consequently, the majority of isolated helices derived from proteins are unstable, unless specif ic side-chain interactions stabilize them.