Jw. Taylor et al., A calorimetric study of the folding-unfolding of an alpha-helix with covalently closed N and C-terminal loops, J MOL BIOL, 291(4), 1999, pp. 965-976
The thermal melting of a dicyclic 29-residue peptide, having helix-stabiliz
ing side-chain to side-chain covalent links at each terminal, has been stud
ied by circular dichroism spectropolarimetry (CD) and differential scanning
calorimetry (DSC). The CD spectra for this dicyclic peptide indicate that
it is monomeric, almost fully alpha-helical at -10 OC, and undergoes a reve
rsible transition from the folded to the disordered state with increasing t
emperature. The temperature dependencies of the ellipticity at 222 nm and t
he excess heat capacity measured calorimetrically are well fit by a two-sta
te model, which indicates a cooperative melting transition that is complete
within the temperature ranges of these experiments (from -10 degrees C to
100 degrees C)This allows a complete analysis of the thermodynamics of heli
x formation. The helix unfolding is found to proceed with a small positive
heat-capacity increment, consistent with the solvation of some non-polar gr
oups upon helix unfolding. It follows that the hydrogen bonds are not the o
nly factors responsible for the formation of the alpha-helix, and that hydr
ophobic interactions are also playing a role in its stabilization. At 30 de
grees C, the calorimetric enthalpy and entropy values are estimated to be 6
50(+/-50) cal mol(-1) and 2.0(+/-0.2) cal K-1 mole(-1), respectively, per r
esidue of this peptide. Comparison with the thermodynamic characteristics o
btained for the unfolding of double-stranded alpha-helical coiled-coils sho
ws that at that temperature the enthalpic contribution of non-polar groups
to the stabilization of the alpha-helix is insignificant and the estimated
transition enthalpy can be assigned to the hydrogen bonds. With increasing
temperature, the increasing magnitude of the negative enthalpy of hydration
of the exposed polar groups should decrease the helix-stabilizing enthalpy
of the backbone hydrogen bonds. However, the helix-stabilizing negative en
tropy of hydration of these groups should also increase in magnitude with i
ncreasing temperature, offsetting this effect. (C) 1999 Academic Press.