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The Nobel Prize in Chemistry 1984
Bruce Merrifield

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Supporting Protein Chains

Creating the proteins that perform the host of tasks necessary to support life is not unlike creating a chain, link by link. In this case, the links, or amino acids, are attached sequentially to the growing chain, or peptide. Once the peptide is made, the chain folds up, either on its own or with others, to form a three-dimensional protein that can carry out its particular task.

What takes minutes or hours to achieve in Nature took months and years to recreate in the laboratory. Attaching amino acids together to form even small peptide chains was a laborious procedure, with chemists faced with the painstaking task of having to continuously fish out the fragile peptide chain from solution before adding each link. Bruce Merrifield's solution for building chains of peptides in any predetermined order was simple, ingenious and radical. He proposed a method in which a molecular anchor provides the foundations for peptide synthesis. By attaching what would be the last amino acid in the peptide to a solid support made from a polymer, amino acids can then be chemically linked one by one in the correct order to generate the growing peptide chain. Once the construction process is completed the peptide can be released from the support.

The elegance of this method is that any by-products and unused starting ingredients that are not attached to the anchored peptide can be easily washed away after each step in the process, increasing yields to staggering levels. Within a few years, Merrifield had automated the peptide construction process, but his method wasn't accepted until he showed it could create fully functioning proteins – from the 9-amino-acid-long peptide hormone bradykinin to his milestone synthesis of an active enzyme, ribonuclease A, created by attaching each of its 124 amino acids individually. His method was later adopted to create designer nucleotides, short fragments of specific sequences of DNA, which meant that Merrifield's breakthroughs in chemistry evolved into an essential tool for molecular biology and biotechnology.

 

This Speed Read is supported by the Camille and Henry Dreyfus Foundation Special Grant Program in the Chemical Sciences.

 

First published 2 April 2009
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