As is well-known, peptides helices can be right or left handed. Many details of structure, amino acid identity and orientation can control this screw sense, and sometimes the controlling factors can be quite subtle. In a JACS communication, Jonathan Clayden (yes, the co-author of the amazing organic chemistry textbook) and his group uncover a surprising factor that controls the helical screw sense and also incorporate a neat "reporter group" to monitor the screw sense.
But this reporter group is nothing fancy and is simply a gycine installed in the middle of a long sequence of amino acids which consists of alpha-aminoisobutyric acid or Aib. Aib is simply alanine with an extra methyl at the alpha carbon. It is well known to impart helical propensities to peptides and has been used several times as a helical 'lock'.
In this case the Gly is in the center of a 20 amino acid peptide where all other residues are Aib. The peptide is clearly helical, but what's the screw sense? That's where the power of NMR spectroscopy comes in. The two protons in Gly are diastereotopic which means that in principle they could have different chemical shifts and signals in the NMR spectrum. In practice though, rapid interconversion between the left and right handed helices leads to an average and gives a single signal in the spectrum.
However if interconversion between the two screw senses could be 'biased' by making the equilibrium constant favor one of them, then one could presumably observe two separate signals for the two Gly protons even if the transition is fast on the NMR time scale. To accomplish this, Clayden et al. do something peculiar; they incorporate a L-Phe residue at the N-terminal of the helix. This group, even if far away from the central Gly, somehow seems to remotely interact differently with each of the two Gly protons. The incorporation of this terminal group leads to a considerable splitting in the signals of the two protons (up to 100 ppm), easily distinguishing them apart. Also for some reason, N-terminal groups seem to work better than C-terminal groups.
The reasons for the transmission of this effect over no less than 27 bonds are not clear, but they probably have something to do with the subtle change in conformational behavior that dictate helix folding. The authors even observe small differences for amide vs ester bonds as capping groups. Finally, they obtain an x-ray structure of this helix which turns out to be a 3/10 helix and confirm their observations.
These days there is a drive to 'tether' certain parts of oligopeptides to lock the resulting conformation in a helical form. Sometimes, even constraining end groups covalently (by metathesis for instance) seems to ensure a critical 'nucleation' structure that then zips up the rest of the helix. The exact percentage of the helix in solution could be a matter for discussion, but this study seems to indicate similiar end-group influenced conformational organization. I thought it was neat and points to further challenges and questions in our understanding of the deceptively simple question, "Why are helices stable in solution"?
Solà, J., Helliwell, M., & Clayden, J. (2010). N- versus C-Terminal Control over the Screw-Sense Preference of the Configurationally Achiral, Conformationally Helical Peptide Motif Aib-Gly-AibJournal of the American Chemical Society DOI: 10.1021/ja100662d