Helix propensities

Avgelj, F., Luo, P., and Baldwin, R. L. (2000). Energetics of the interaction between water and the helical peptide group and its role in determining helix propensities. Proc. Natl. Acad. Sci. USA97, 10786-10791. 

Helix propensities have been measured by different groups for all 20 proteinogenic amino acids using statistical surveys of protein helices/8,91 host-guest analysis/101 small model peptides and protein fragments/11-141 site-directed mutagenesis/151 and calculation studies/16171 The results from each method are different, although some correlations can be made. 

Measured s values (helix propagation factor values) obtained by various groups110,12,24-311 for all the amino acids are listed in Table 1. Chakrabartty and Baldwin1281 have also compared free-energy changes and determined rank orders of helix propensities of all the amino acids as measured in various experimental peptide systems. 

For further information on C -disubstituted glycines, see also Section 10.3. a-Amino-isobutyric acid (Aib, 1) (Scheme 2), also known as C -methylalanine, is the prototype of the class of residues termed C -disubstituted glycines. It is also the nonproteinogenic a-amino acid with the highest helix propensity. Aib has two methyl groups on the a-carbon. The extra methyl group severely limits the possible 4> and i) values, such that allowed regions of... 

Persikov, A. V., Ramshaw, J. A., Kirkpatrick, A., and Brodsky, B. (2003). Triple-helix propensity of hydroxyproline and fluoroproline Comparison of host-guest and repeating tripeptide collagen models./ Am. Chem. Soc. 125, 11500-11501. 

Interestingly, the high a-helix propensity of (5)-ll has been observed in the X-ray structures of both tripeptides (see Table 1) and 9-mer peptides (Table 2). The molecular structures of the terminally blocked 9-mer peptides 31 and 32 were determined by X-ray diffraction and the observed < >P angles are shown in Table 2. For comparison, the similar peptide containing Aib at position 2 (30) is also listed in Table 2. In all three peptides, the succession of similar pairs of / F values correspond to an a-helical conformation. 

As mentioned above, these three subunits were designed to form a first a-helical turn in which the four amide groups are ideally oriented to participate in the H-bond network of an a-helix. Peptides that are linked to these templates adopt an a-helical conformation due to the conformational constraint induced by the high inherent a-helix propensity of the template and the H-bond network that is initiated by the proper orientation of the carbonyl groups. Thus, helix induction is achieved by the combination of steric and electronic properties of the three subunits. 

In order to show that HIT-1 was a-helix compatible and induces a-helical conformations in short peptides from the N- and C-terminus as well as from internal positions, template-linked peptides have been compared to nonconstrained reference peptides. In the N- and C-cap projects a hydrophobic 12-mer peptide was used as a standard reference. The 12-mer reference peptide 104 was originally developed for host guest experiments to evaluate the a-helix propensities of unnatural amino acids (see Section II.A) and had later been used to confirm N-cap induced helix formation.141,202,214 In the C-cap series and for position-independent templates the same reference peptide could be used after minor modification of the terminal protection groups. The suitably protected reference peptide and the corresponding template-linked model peptides used for the evaluation of N-terminal, C-terminal, and internal helix induction are depicted in Figure 39. 

Exploring a-helix formation as a function of peptide primary structure enabled Jarrold and coworkers to establish intrinsic helix propensity data for a... 

Chiu, H. P., Suzuki, Y., Gullickson, D., etal. (2006) Helix propensity of highly fluorinated amino acids. Journal of the American Chemical Society, 128(49), 15556-15557. 

Chakrabartty, A., Kortemme, T. and Baldwin, R. L. (1994) Helix propensities of the amino acids measured in alanine-based peptides without helix-stabilizing side-chain interactions. Protein Science, 3(5), 843-852. 

M. Blaber, X.-J. Zhang, and B. W. Mathews Structural basis of amino acid a-helix propensity. Science 2, 1637 (1993). 

Creamer et al. have shown a strong correlation between decreased helix propensity of amino acid residues and the entropic effects of holding a valine or isoleucine residue in an a-helical conformation (185). This results from the limitation on %1 values of the (3-branched amino acids imposed by the helical backbone conformation. 

The helix formation would be more likely in the hydrophobic medium. Water molecules would compete with peptide backbone NH and C=0 groups for hydrogen bond formation this competition would reduce the relative helix propensity in water. Additionally, the isolated NH and C=0 groups would be quite unstable if not hydrogen bonded in a hydrophobic medium, and so would be driven to maximize their participation in hydrogen bonds. 

J. Hermans, A. G. Anderson, and R. H. Yun, Biochemistry, 31,5646 (1992). Differential Helix Propensity of Small Apolar Side Chains Studied by Molecular Dynamics Simulations. 

Barlow DJ, Thornton JM (1988) Helix geometry in Proteins. J Mol Biol 201(3) 601-619 Pace CN, Scholtz JM (1998) A helix propensity scale based on experimental studies of peptides and proteins. Biophys J 75(1) 422 27... 

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