Amphipathic control of the 3₁₀‐/α‐helix equilibrium in synthetic peptides

Abstract

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.

Molecular Basis of Agonistic Activity of ERα17p, a Synthetic Peptide Corresponding to a Sequence Located at the N-Terminal Part of the Estrogen Receptor αLigand Binding Domain

“…dmol -1 ) were found. Conversion of statistical-coil into α-helix was estimated complete in the presence of TFE (from the equation: % α-helix = -100([ ] 222 +3000)/33000 [26,27]). …”

Stabilisation of a short α‐helical VIP fragment by side chain to side chain cyclisation: a comparison of common cyclisation motifs by circular dichroism

“…Because of the additional positive maximum recorded at 197 nm [(θ) = 7947 deg cm 2 dmol À1 ] and the local negative shoulder at~220 nm [(θ) = À10 477 deg cm 2 dmol À1 ], helix structure is likely. The fact that the intensity of the band at~220 nm is smaller to the one at 205 nm suggests the formation of a 3 10 helix, confirming the role of Aib in this context [33,34]. It is noteworthy that the low intensity of the band at 197 nm is also in favour of 3 10 helix [16,35,36].…”

“…Recently, Manning and Woody have provided convincing simulation data concerning the 3 10 -helix CD signature [33]. More precisely, they showed that 3 10 [35,34]. More precisely, the values would be 0.20 < R < 0.40 in the case of 3 10 helix and 0.85 < R < 0.90 in the case of the a-helix [39,40].…”

“…Recently, Manning and Woody have provided convincing simulation data concerning the 3 10 ‐helix CD signature [33]. More precisely, they showed that 3 10 ‐helix is characterised by an intense 208 nm band relative to the 222 nm band, in contrast with an α ‐helix . Indeed, the α ‐helix is usually characterised by a strong positive maximum at ~ 190 nm and two negative bands at 208 nm and 222 nm.…”

“…proposed to use the ratio R = [ θ ] 222 /[ θ ] 208 (i.e. [ θ ] n→π* /[ θ ] π→π* ) to detect a 3 10 ‐helix: R ≤ 0.4 in the case of 3 10 helix and R ≈ 1 in the case of α ‐helix . More precisely, the values would be 0.20 < R < 0.40 in the case of 3 10 helix and 0.85 < R < 0.90 in the case of the α ‐helix .…”