Amphipathic control of the 3(10)-/alpha-helix equilibrium in synthetic peptides.

A series of short, amphipathic peptides incorporating 80% C(alpha),C(alpha)-disubstituted glycines has been prepared to investigate amphipathicity as a helix-stabilizing effect. The peptides were designed to adopt 3(10)- or alpha-helices based on amphipathic design of the primary sequence. Characterization by circular dichroism spectroscopy in various media (1 : 1 acetonitrile/water; 9 : 1 acetonitrile/water; 9 : 1 acetonitrile/TFE; 25 mM SDS micelles in water) indicates that the peptides selectively adopt their designed conformation in micellar environments. We speculate that steric effects from ith and ith + 3 residues interactions may destabilize the 3(10)-helix in peptides containing amino acids with large side-chains, as with 1-aminocyclohexane-1-carboxylic acid (Ac(6)c). This problem may be overcome by alternating large and small amino acids in the ith and ith + 3 residues, which are staggered in the 3(10)-helix.

Two cyclohexanespiro-5'-hydantoin monohydrates.

Cyclohexanespiro-5'-hydantoin monohydrate, C8H12N2O2.H2O, has a chair-shaped cyclohexane ring with endocyclic torsion-angle magnitudes in the range 54.4 (2)-56.3 (2) degrees. All potential hydrogen-bond donors are involved in intermolecular hydrogen bonding, with lengths in the range 2.760 (2)-2.908 (2) A. In its indolyl adduct, 2-(3-indolyl)cyclohexanespiro-5'-hydantoin monohydrate, C16H17N3O2.H2O, the cyclohexane moiety adopts a chair conformation with the indolyl substituent in an equatorial position. The N-H portion of the hydantoin ring is cis to indolyl, while the C=O of the hydantoin is trans. Endocyclic torsion-angle magnitudes of the cyclohexane ring are in the range 54.2 (2)-56.7 (2) degrees. All potential hydrogen-bond donors are involved in intermolecular hydrogen bonds, with lengths 2.828 (2)-3.187 (2) A.