large nucleoli and may even have more than one nucleolus. The cell nucleus is the site
of the storage and replication of most of the cell’s hereditary information.
The three components of cellular structure offer a plethora of druggable targetsfor
the drug designer. The most important of these components is the cell membrane. Drugs
are designed to interfere with the functioning properties of the cell. The cell membrane
is ideally suited to enabling such an opportunity. The normal communication of signals
from the extracellular environment to the intracellular environment within a given cell
(thereby regulating biochemistry within that cell), or the communication of signals
from one cell to the next cell (thereby regulating the biochemistry of adjacent cells), is
all mediated by macromolecular proteins (e.g., ion channel proteins, G proteins) within
the cell membrane. The macromolecular constituents within the membrane structure are
all important targets for drug design.
Although the cytoplasm contains many extremely important organelles, it is some-
what less important as a source of cellular components as druggable targets. This may
arise from the importance of these organelles to the life of the cell. Mitochondria, for
example, are the energy sources for the cell. Any interference with mitochondrial func-
tion could easily result in rapid cell death; cyanide (CN-), for example, kills by poi-
soning the electron transport chain within mitochondria. Accordingly, targeting such an
important organelle for drug design is fraught with the associated problems of toxicity.
The cytoplasm does contain a number of smaller molecules that are involved in cellu-
lar biochemistry. For instance, the cytoplasm is a rich source of chemical catalysts (e.g.,
protein enzymes) and chemical mediators (e.g., lipid-derived eicosanoids). These
chemicals are an important source of drug targets; however, since they are not neces-
sarily associated with a particular organelle or cellular structure, they will be discussed
separately in chapter 8.
The cell nucleus is another important source of druggable targets. Surprisingly, the
nucleus is not as important to the survival of an individual cell as are many of the cyto-
plasmic organelles. A cell can live without its nucleus, it just cannot reproduce. (Mature
adult human red blood cells, for example, do not have nuclei.) On the other hand, a cell
cannot live without its mitochondria. Therefore, the cell nucleus is an important struc-
ture to target when designing drugs for diseases in which one wishes to stop cellular
reproduction (e.g., cancer, viral or bacterial infections).
This chapter discusses potential drug targets in each of the main components of cel-
lular structure, starting with the cell membrane and working inwards to the cell nucleus.
7.2 Targeting Cell Membrane Structures: Lipid Component
Our present ideas about the nature of biological membranes, which are so fundamental
to all biochemical processes, are based on the Singer–Nicholson mosaic model. This
model of the membrane is based on a phospholipid bilayer that is, however, asymmet-
rical. In the outside monolayer,phosphatidylcholine (lecithin) predominates, whereas
the inner monolayer on the cytoplasmic side is rich in a mixture of phos-
phatidylethanolamine, phosphatidylserine, and phosphatidylinositol. Cholesterol mole-
cules are also inserted into the bilayer, with their 3-hydroxyl group pointed toward
the aqueous side. The hydrophobic fatty acid tails and the steran skeleton of cholesterol
ENDOGENOUS CELLULAR STRUCTURES 409