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Naturally Occurring Polymers—Animals 373

does not have a core structure but rather undergoes dramatic structural rearrangements as it oper-
ates. Ribosomes, by comparison have two RNAs and a few proteins adapting only several major
conformational changes are it performs its functions. Further, spliceosomes morph into different
compositions as they carry out their tasks. Thus, one team of RNA and protein may complex with
an intron and then fall away with other members being added and deleted to the spliceosome as
additional tasks are performed. Yet, the chemistry that is performed by the spliceosome is generally
simple involving two transesterfication reactions cutting each end of the intron, and then forming one

phosphodiester bond between the adjoining exons.
The reason for the complexity of the spliceosome is believed to be regulation. The spliceosome
must respond to changes in the needs of a cell. It must not only perform many jobs but it must do
them on a tight time scale.

10.13 PROTEOMICS

Identification of the protein target that interacts with a molecule is a bottleneck in drug discovery.
Here we will deal with one branch of this important venture.
Probably for defensive reasons, because of the overwhelming amount of information, possi-
bilities, and techniques required, subdivisions are present so that some groups focus on protein
structures, others on DNA structures, others on the interaction between the two, others on target

molecules/sites, and still others deal with specific diseases or biological responses. One such sub-
division has been given the name “Proteomics” that deals with the interfacing or bridging between
genomics or gene information and drug or target molecule activity. While we have uncovered more
than 75,000 sequences of the human genome, we have just begun to look at this “raw” information
for actual active or target sites. We need to remember that we are looking at the master template, the
DNA genome, its interactions with various proteins at each of the real and potential sites of action,

and fi nally target sites and molecules to effect specific biological responses. Let us remember that
this is polymer science in its truest form.
Almost three quarters of the known proteins have no known cellular function but as we have
learned in the past, nature seldom has true “junk” in its biological pile of macromolecules. In
addition to identifying specifi c target and target molecules, other discoveries are important such

as new enzymes, signaling molecules, pathways, and finally mechanistic behaviors and factors.

Identification of such factors will allow better drug discovery and activity downstream.
Factors that will be needed in this hunt include the following: First, there is needed a more
complete understanding of the behavior of particular proteins. This includes such seemingly pedes-
trian, but critical, activities as providing pure and structurally and chemically unaltered proteins.
This “unaltered” form includes conformational as well as confi gurational aspects. It is known that
proteins and protein fragments may be misfolded when reproduced employing a variety of repro-
ductive techniques. These wrong structures can cause incorrect test results and when present as part
of a large data bank, point the scientist in the wrong direction, or alternately, not point them in the
right direction.
Second, while each of us have more than 100,000 proteins, only a fraction is expressed in
any given cell type. Thus, it is a complex and puzzling problem to accurately match protein
activity to some biological response. One emerging tool is to measure the relative abundance
of mRNA in a cell because there is a not unexpected relationship between protein concentra-
tion and mRNA concentration. However, these correlations do not always follow, sometimes
because the regulatory processes occur after transcription, so that caution must be exercised.
Thus, the direct measure of the concentration of the particular protein is a better measure. Such
protein determination is often achieved by traditional analytical tools such as coupling some
chromatography technique such as electrophoresis with MALDI (mass spectrometry). Other
biological techniques are employed and sometimes these are coupled with traditional analytical
techniques.

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