198 Topics in Current Chemistry Editorial Board: A. de Meijere KN ...

Supramolecular Synthons and Pattern Recognition 79
additional C(2)-H◊◊◊O(2) and C(8)-H◊◊◊O(2) interactions forced by the geometry
of the A.T/U base pair (Scheme 12). Moreover, the repulsive secondary
interaction between the O(2) atom of T/U and N(1) or N(7) atom of A is now
balanced by a stabilising hydrogen bond. In recognition motifs where the
C-H◊◊◊O hydrogen bond is a viable contributor, the hydrogen bonding abilities
of thymine and uracil must be considered in a different light. The sp 2 C-H of
uracil has a greatly enhanced hydrogen bonding capability compared to the CH 3
hydrogens of thymine because of its higher acidity. It has been shown that the
geometries and energies of DNA base triplets (CG):C, (TA):T, (AT):A and
(GC):G and their matching in the homologous recombination can be explained
by the auxiliary C-H◊◊◊O and C-H◊◊◊N hydrogen bonds [58]. It is clear that
C-H◊◊◊O and C-H◊◊◊N hydrogen bonds are abundant in biological macromolecules
and despite their small enthalpic contribution (0.5–2.0 kcal mol –1 ) [59],
they seem to exert pronounced structural and functional effects [60].
7.2
Pattern Recognition in Drug-Enzyme Binding
The idea of recognition between enzyme and substrate goes back more than one
hundred years to Fischer’s “lock-and-key” analogy of enzyme catalysis [61].
Drug-receptor recognition and binding is, however, not as simple as the lockand-key
analogy and may be more likened to a hand fitting into a glove. Both the
drug (or ligand) as well as the receptor (or active site) are flexible and yet have
very specific requirements for mutual recognition [62]. It is important to note
that the docking of a drug molecule into the active site of a receptor protein is
governed by the same combination of forces that control crystallisation, namely
electrostatic forces, hydrogen bonding interactions, van der Waals forces and
hydrophobic effects, the last factor being responsible for the exclusion of water
a b
c d
Scheme 12 a – d. C-H◊◊◊O hydrogen bonds in: a Watson-Crick U . A pair; b Hoogsteen T . A pair;
c O8G◊ A pair (O8G: 7,8-dihydro-8-oxoguanine); d Hoogsteen C + ◊ G pair. For patterns a, b
and c, see [57]; pattern d is putative