Alpha Helix

The alpha helix is the commonest ordered conformation of a peptide backbone: a right-handed coil in which each carbonyl oxygen hydrogen-bonds to the amide hydrogen four residues further along. The geometry is fixed rather than approximate, with roughly 3.6 residues per turn, a rise near 1.5 angstroms per residue and a pitch near 5.4 angstroms. Every hydrogen bond points the same way, giving the helix a net dipole.

Helices matter because several receptor families read them. The class B G protein-coupled receptors binding GLP-1, GIP, GHRH and calcitonin all engage a helical ligand, the helix docking into a large extracellular domain while the peptide's amino end enters the transmembrane core. Short peptides of this kind are largely disordered in plain buffer and fold only on binding, which is why their circular dichroism spectra in water often show a random-coil trough near 200 nanometres rather than the paired minima near 208 and 222 nanometres a helix produces.

Because helicity and affinity travel together, stabilising the helix is a standard design move. Hydrocarbon staples, lactam bridges between side chains four positions apart and alpha-aminoisobutyric acid substitutions pre-organise the chain so less entropy is paid on binding, and the resulting rigidity usually buys protease resistance too, since most endopeptidases need an extended backbone. Alanine and leucine favour the helix; proline cannot form it at all.

The recurring error is treating a drawn or predicted helix as a measured one. A helical wheel diagram, a structure-prediction model and a vendor claim of an alpha-helical peptide all describe what a sequence could do. Percent helicity from circular dichroism run in trifluoroethanol is a different number from helicity in aqueous buffer, often by a large factor, and only the aqueous value governs behaviour before the receptor is reached.