The Nobel Prize in Chemistry 1957
Lord Todd
Presentation Speech by Professor A. Fredga, member of the Nobel Committee for Chemistry of the Royal Swedish Academy of Sciences
Your Majesties, Your Royal Highnesses,
Ladies and Gentlemen.
Nucleotides and nucleotide coenzymes are words that may seem
strange and abstruse, but these compounds are of great importance
to all of us. We have such substances everywhere in our bodies
and they regulate many of the processes of life. The term is
derived from nucleus, which here refers to cell-kernels or
nuclei. The Nobel Prize of this year has nothing to do with
atomic nuclei, nuclear fission or hydrogen bombs. Nucleotides are
regularly found in the chromosomes of the cell-kernels, where they
are connected with the units of heredity, but also in the cell
plasma. In combination with proteins they constitute the virus
molecules and many coenzymes are nucleotides of low molecular
weight but with a special structure. Thus they are a group of
substances of very great biological importance, perhaps the most
important of all.
The nucleotides have been known for nearly 90 years and they have
been frequently studied by both chemists and biologists, but for
a long time they were, from the chemist's point of view, an
underdeveloped field of research. The difficulties were too
great. Gradually it was established that they are built up of
three different kinds of "building-stones" of quite different
chemical character: phosphoric acid, a sugar, and a heterocyclic
base containing nitrogen. I cannot express it more popularly,
except to mention that these bases are compounds related to
caffeine. Two different sugars are found, ribose and
desoxy-ribose, and about half a dozen different bases. The simple
building-stones may then be combined in hundreds or thousands to
form macromolecules, the nucleic acids.
It is, however, not enough to know the building-stones; we must
also know how they are connected to each other. The
building-plan, the pattern or whatever you prefer to call it,
must be very essential for the behaviour of the macromolecule in
chemical and biological processes. The sugars and the
heterocyclic bases are both somewhat complicated molecules, which
may be connected to each other in several different ways, and
finally it must be established how the phosphoric acid is bound.
The task is very difficult; the combination of three quite
different kinds of building-stones in one macromolecule gives it
a very special character and neither the traditional methods of
organic chemistry, nor those of inorganic chemistry are directly
applicable. It is, however, pre-eminently a task for an organic
chemist, and for more than ten years Sir Alexander Todd has held
a leading position in this field.
Some idea of the building-plan may be obtained by examining the
products formed by partial degradation of the macromolecule into
small fragments containing a limited number of building-stones.
Conclusive evidence can, however, only be obtained by synthetic
methods, by building up possible combinations of sugars and bases
- with or without phosphoric acid and comparing them with the
degradation products. It is of course imperative to use such
methods that the structure of the synthetic products is
irrefutable.
The work has been very comprehensive, and many special methods
have been evolved, but it is hardly possible to give a
non-chemist a clear idea of the brilliant experimental work
accomplished. Perhaps I should specially mention the methods for
introducing phosphoric acid, the phosphorylation. In recent
years, the fundamental role of phosphoric acid in the biochemical
processes has become more and more evident, and the new
phosphorylation methods - now approximating to those used in the
biosynthetic procedures - are also of interest outside the
special domain of nucleotide chemistry.
The building-plan of the nucleic acids is now established, at
least in its outlines. We have a long chain, where the links are
alternately sugar and phosphoric acid, and to each sugar molecule
is attached a heterocyclic base as a small pendant. Thus there is
an equal number of acid and basic groups. The different
building-stones are always connected according to the same
pattern and the difference between various nucleic acids must
therefore be due to the kinds of bases and their relative
arrangement. The number of different types is small - in a
certain chain usually only four different bases occur - but in a
macromolecule with thousands of appendant base molecules the
number of possible combinations must be very great. We are
familiar with the coding potentialities of the Morse alphabet,
which has only two symbols, dots and dashes.
Through Sir Alexander's work a solid foundation is laid for the
future development in this field. Starting from this work, other
scientists have advanced very fascinating theories as to the
arrangement of the chains; it seems that they may be coiled up as
a helix with the bases inside. This model can perhaps explain how
a nucleic acid chain can bring about the formation of another
similar chain or even of a protein. We are here approaching very
fundamental biological questions.
The synthetic methods have also been successfully applied to the
preparation of low-molecular nucleotide coenzymes, for instance
the cozymase, which plays a part in alcoholic fermentation and other
biochemical processes. The ways are now open for synthetic preparation
of the different types occurring in nature. It is also possible
to synthesize coenzymes with slightly modified structure and study
the effect of these modifications on the activity, and hence gain
better insight into the mode of action of the enzymes.
Sir Alexander Todd. Some fifteen years ago
you started your work in nucleotide chemistry. You saw the great
importance of this topic and you did not underrate the
difficulties. Today the chemical structure of these compounds is
established - in any case in its outlines - and a solid
foundation is laid for future work by biochemists and biologists.
Results of utmost interest have already been reported and others
will follow.
An organic chemist is perhaps most impressed by your studies in
phosphorylation. We know today that phosphoric acid is engaged in
most biochemical processes, but we know rather little of how it
works. Some years ago, you expressed the opinion that the methods
used by the living organism owe their air of magic largely to our
lack of knowledge of the simple chemistry of the esters of
phosphoric acids. You have learned to handle these esters with
amazing skill, and I am sure that in due time the air of magic
will disperse.
In recognition of your services to chemistry and to natural
science as a whole, the Royal Swedish Academy of Sciences has
decided to bestow upon you the Nobel Prize for Chemistry for your
work on nucleotides and nucleotide coenzymes. To me has been
granted the privilege of conveying to you the most hearty
congratulations of the Academy, and of inviting you to receive
your prize from the hands of His Majesty the King.
From Nobel Lectures, Chemistry 1942-1962, Elsevier Publishing Company, Amsterdam, 1964
Copyright © The Nobel Foundation 1957
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