ISSN:
0887-3585
Keywords:
helix stabilization
;
helix dipole
;
charged group
;
pH titration
;
electrostatic interaction
;
hydrogen bonding
;
Chemistry
;
Biochemistry and Biotechnology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Medicine
Notes:
Interactions between the α-helix peptide dipoles and charged groups close to the ends of the helix were found to be an important determinant of α-helix stability in a previous study.1 The charge on the N-terminal residue of the C-peptide from ribonuclease A was varied chiefly by changing the α-NH2 blocking group, and the correlation of helix stability with N-terminal charge was demonstrated. An alternative explanation for some of those results is that the succinyl and acetyl blocking groups stabilize the helix by hydrogen bonding to an unsatisfied main-chain NH group. The helix dipole model is tested here with peptides that contain either a free α-NH3+ α-COO- groups, and no other charged groups that would titrate with similar pKa's. This model predicts that α-NH3α-COO- groups are helix-destabilizingand that the destabilizing interactions are electrostatic in origin. The hydrogen bonding model predicts that α-NH3 and α-COO- groups are not themselves helix-destabilizing, but that an acetyl or amide blocking group at the N- or C- terminus, respectively, stabilizes the helix by hydrogen bonding to an unsatisfied main-chain NH or CO group.The results are as follows: (1) Removal of the charge from α-NH3 and α-COO- groups by pH titration stabilizes an α-helix. (2) The increase in helix stability on pH titration of these groups is close to the increase produced by adding an acetyl or amide blocking group. (3) The helix-stabilizing effect of removing the charge from α-NH3 and α-COO- groups by pH titration is screened by increasing the NaCl concentration, and therefore the effect is electrostatic in origin. (4) Replacing the C-terminal amide blocking group with a methylester blocking group, which cannot donate a hydrogen bond, causes little change in helix stability.
Additional Material:
6 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/prot.340050102
