Specific hydrogen-bonding patterns

Since this book provides a wide selection of relevant topics presented by some of the major actors in the domain, we shall emphasize here the conceptual and prospective aspects, illustrated by a brief retrospective of our own work. It started with the exploration of the concept of supramolecular polymers, introduced in 1990 [3a], through the implementation of the principles of supramolecular chemistry to generate polymers and liquid crystals of supramolecular nature from molecular components interacting through specific hydrogen-bonding patterns. The chemistry of supramolecular polymeric entities based on these as well as on other types of noncovalent interactions has since then actively developed [3-17]. 

In a 1 2 ratio these compounds yield a mixture of (Z/Z), (EIE) and (E/Z) isomers plus a substantial amount of the (E) and (Z) isomers of the monohydrazone monoketone. The complexity of the mixture (due to several equilibria that are established between its components) was illustrated by its complex H NMR spectrum. However, addition of one equivalent of barbiturate to the mixture led to a dramatic simplification of the NMR spectrum with the disappearance of the different products and the emergence of a single new species. This remarkable simplification of the spectrum is a consequence of the templating effect played by the barbiturate that amplifies the formation of only one of the receptors - in this case the ZyZ isomer. Interestingly, the addition of other species to the mixture such as acetate or 1-benzyluracil (with similar pKa values to barbiturate but different hydrogen bonding patterns) did not lead to the amplification of any specific species. 

The use of conserved residues to maintain the main-chain interactions along the substrate backbone makes differentiation of the MMPs through these interactions difficult. Instead, differences in the regions where the side chains of the substrate interact can be used to drive the discovery of specific MMP inhibitors. The hydrogen-bonding pattern also indicates that right-hand side (P -... 

Figure 4 Substitution of fys4 with 2-hydroxylethyl-cysteine in the X-repressor changes the hydrogen-bonding pattern and DNA substrate specificity from C G to T A.

A second example that illustrates the power of exhaustive conformational searching is foimd in the recent analysis of glycine terminated helices (Gly at C) (2). Specifically, two recurrent motifs are observed in a-heHces terminated by a glycine (Figure 1). In each, the glycine residue adopts a left-handed conformation (i.g. ( )>0). In one case, termed the Schellman motif, a distinctive, doubly hydrogen bonded pattern between backbone partners, consisting of 6 1,5 2... 

---