amino acid composition. These proteins hydrogen-bond to the prism face of ice crystals,
inhibiting crystalline growth. These peptides are 300 times more effective in preventing
freezing than conventional organic solvent antifreezes. From the perspective of drug
design, antifreeze proteins could be exploited for purposes of cryopreservation, pro-
longing the effective “shelf-life” of organs removed for donation and transplantation.
Also, understanding the mechanism of antifreeze proteins may help drug design for
human diseases involving biocrystallization. These disorders include gout, kidney
stones, and gallstones. If one could exploit the prism face of a crystal as a potential
receptor, and then design drugs to bind to the crystal face, it might be possible to retard
crystal growth, thus preventing stone formation.
8.3.2.2 Snail Conotoxins and Drug Design
Conotoxins are small (10–30 amino acids), disulphide-rich, conformationally constrained
peptides produced by marine mollusks such as cone snails. The fish-hunting snails, in
particular Conus geographus, have been extensively studied. Depending upon the
arrangement of disulphide bonds and the number of residues between cysteines, five or
more classes of conotoxin can be structurally identified:
- Alpha class (e.g., alpha conotoxin G1)
- Mu class (e.g., mu conotoxin GIIIA)
- Omega class (e.g., omega conotoxin GVIA)
- Delta class (e.g., delta conotoxin TxVIA)
- Kappa class (e.g., kappa conotoxin PVIIA)
These various conotoxins enable the snail to paralyze fish that it is hunting. The cono-
toxins bind to various voltage-gated ion channels, unlike endogenous ligands found in
humans. Thus the conotoxins present a unique opportunity to design drugs capable of
binding to voltage-gated ion channels. Mu conotoxins can block the voltage-gated Na+
channel, while omega conotoxins can inhibit the voltage-gated Ca^2 +channel. The cono-
toxins can also differentiate between types of voltage-gated Ca^2 +channels, including the
L-, N-, and P-type channels. Because they are conformationally constrained bioactive
peptides, they are a good point for the initiation of drug design.
8.4 Nucleic Acids as Drugs and Drug Design Targets
Nucleic acids are obvious drug design targets, offering important receptors around which
to design drugs. Drugs targeting various aspects of nucleic acid replication, transcription,
and translation have obvious applications as agents with which to treat cancer or infectious
diseases; these are presented in chapters 7 and 9, respectively, and will not be repeated here.
Nucleic-acid-related molecules (nucleotides, nucleosides, purines, pyrimidines) may
also be used as drugs themselves (and not only as drug receptors). Once again, as discussed
in chapters 7 and 9, this is most relevant in the areas of cancer and infectious disease,
with purine/pyrimidine analogs being exploited as antimetabolites. 5-Fluorouracil is a well-
describedantineoplastic agent. Analogously, 5-fluorocytosine is used as an antifungal
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