Biomedical Engineering Reference
In-Depth Information
Learning from Proteins and Drugs: Receptors
That Mimic Biomedically Important Binding
Motifs
Fraser Hof and Thomas Pinter
Abstract Proteins are highly evolved, sophisticated machines which function
together to maintain homeostasis in their hosts. While merely a collection of
amino acids covalently bonded in a specific sequence, their wide variety of
functions is truly remarkable. Of course these covalent sequences are essential for
proper function, but equally important for proper function are
weak
interactions:
protein folding, enzyme-substrate interaction, and protein-protein communication
are all controlled by forces weaker than covalent bonds and understanding these
forces is fundamental in medicinal chemistry and drug design. Many inhibitory
drugs mimic natural substrates for protein binding sites but inhibition of
the substrate by mimicking the binding site is also possible. This mimicry and the
biological consequences are under investigation.
Keywords Aromatic interactions, Cation-pi interactions, Host-guest chemistry,
Hydrogen bonds, Molecular Recognition
Contents
1 Introduction: Weak Interactions ............................................................. 34
2 Anion Recognition by Carboxylic Acid Bioisosteres ....................................... 36
3 Receptors That Mimic Natural Aromatic Cage Motifs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
F. Hof (
*
) and T. Pinter
Department of Chemistry, University of Victoria, Victoria, BC, Canada V8W 3V6
e-mail:
fhof@uvic.ca
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