Hello and welcome to Module IV.
In Module IV, what we’ll be doing is taking
a number of different modules: Modules I,
II and III, bringing them together so that
we can see the biological and, hopefully,
medical application of some of those principles
which we’ve learnt.
We’re going to start off by looking at basic
biochemical interactions to best understand
the concept of receptors as drug targets.
Specifically, we’ll be looking to introduce
the concept of agonists and antagonists of
And consider receptors not just as enzymes
which, as we will see, facilitate the changes
in matter or the conversion of one molecule
into more than one molecule or, sometimes,
just its functional alteration. But also,
we’ll be looking at the types of interaction.
And this is where the functional group comes
If you recall from Module III, what was so
important is that you understood the basics
of the individual functional groups, everything
through from carbonyl compounds through to
amides. And this is vital in terms of understanding
the types of interaction which drugs may make
with their targets be they, for example, enzymes
receptors or indeed some of these macro-molecular
structures that you find, such as DNA.
We’ll also be considering the role of water
in drug-receptor binding and furthermore,
considering the impact of this on the thermodynamics
and entropy of the interaction as well.
Also, we’ll be considering the roles of
confirmation and shape. So, this is not just
about the electron density at a particular
part facilitating the best interaction, but
also, as we will see, the shape which forces
the adoption of the best possible orientation
for receptor binding.
So, when we go back in history, when researchers
first began to isolate active ingredients,
most different things like plants or, occasionally,
from purified water organisms such as plankton
and so on so forth, it was not known how they
exerted their effects specifically on the
body. It was known that they had an effect,
but it wasn’t sure what or why or how the
effect was mediated.
Gradually, chemical structure came to be linked
to biological activity. And this is something
called structure-activity relationship. By
varying the structure, we can actually alter
the biological activity of our putative drug
or indeed, our lead compound as a putative
For example, it was discovered that certain
compounds, aromatic ones as well, with a quaternary
amine were often found to either relax or
contract a muscle. If you look at the bottom
right hand side near the microscope, you’ll
see that there is an example here of a quaternary
Note, the difference between a tertiary and
a quaternary is, in this case, you have a
permanent positive charge. This is conveyed
by the complete loss in the formation of a
sigma bond of the lone pair of electrons on
the nitrogen. Quaternisation, which is the
process by which this is achieved, can be
accomplished via a number of different ways.