Templates for a-Helix Stabilization

The versatility of this template was demonstrated with the synthesis of very short unusually helical polyalanine sequences stabilized by chaotrophic anions [35] and host systems for evaluation of the C-terminal helix capping propensities for nonpolar natural amino acids [36]. As model sequences WK4lnp2,LG-Hel-Ag-NH2 for the primary C-terminal amide and WK4Inp2 LG-Hel-A8-X-Inp-NH2 for candidate amino acids X were selected. In these sequences, Hel is the previously mentioned N-terminal helix template, Inp is 4-carboxypiperidine and L is tert-leucine. In the N-terminal region tryptophan (W) provides a UV reporter, four lysines (K4) are solubilizers, and Inp2 L a spacer element. The C-capping test region of these peptides is G-Hel-Ag-X-Inp, and its helicity is taken as proportional to [6)222, the per-residue ellipticity derived from CD analysis [37]. 

Hanessian, G. McNaughton-Smith, H.-G. Lombart, W. D. Lubell, Tetrahedron 1997, 53, 12789-12854. 

Maison, A. Lutzen, M. Kosten, I. Schlemminger, O. Westerhoee, J. Martens, J. Chem. Soc. Perkin Trans. 

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