Relationship of sidechain hydrophobicity and α-helical propensity on the stability of the single-stranded amphipathic α-helix
| Autor: | Oscar D. Monera, Terrance J. Sereda, Nian E. Zhou, Cyril M. Kay, Robert S. Hodges |
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| Rok vydání: | 1995 |
| Předmět: |
Protein Denaturation
Stereochemistry Peptide Biochemistry Protein Structure Secondary Protein structure Drug Stability Structural Biology Drug Discovery Amphiphile Molecule Thermal stability Amino Acids Molecular Biology Pharmacology chemistry.chemical_classification Molecular Structure Organic Chemistry Temperature General Medicine Amino acid chemistry Amphipathic Alpha Helix Helix Thermodynamics Molecular Medicine Peptides |
| Zdroj: | Journal of Peptide Science. 1:319-329 |
| ISSN: | 1099-1387 1075-2617 |
| DOI: | 10.1002/psc.310010507 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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