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amino acids incorporated into proteins may contain are often so short (less than 50 amino acids) that
sugars, nucleophiles (electron donors), electrophiles they are referred to as peptides, oligopeptides, or
(electron acceptors), crosslinkers (a chemical com- polypeptides, and not as proteins. (A protein is re-
pound that forms covalent bonds between adjacent garded as a long polypeptide, generally at least over
polymer chains that lock the chains in place), or al- 80 amino acids in length and usually much longer.)
tered shapes and sizes. Detailed studies on ion chan- Those with novel properties, such as an ability to
nels with over 60 nonnatural amino acids incorpo- bind to a specific ligand (a unique molecule that is
rated illustrate the chemical power of this approach. usually small) are then selected. In these instances,
Minimalist proteins. Proteins are usually large the sequences of the peptides are created de novo
molecules composed of several hundred or even and are not based on that of a naturally occurring
more than a thousand amino acids. Yet, the portion of protein. See GENE; GENE ACTION; GENETIC CODE; PEP-
the protein responsible for a specific biological activ- TIDE. Karla L. Ewalt; Paul Schimmel
ity is usually concentrated in a small part of the struc- Bibliography. J. A. Branningan and A. J. Wilkinson,
ture. In these circumstances, there are advantages Protein engineering 20 years on, Nature Rev. Mol.
to creating a minimalist protein having enough of Cell Biol., 3:964–970, 2002; J. Lippincott-Schwartz
the structure to retain the desired activity. A smaller and G. H. Patterson, Development and use of fluores-
protein is often superior for analyzing and manipulat- cent protein markers in living cells, Science, 300:87–
ing structure-function relationships, and the reduced 91, 2003; S. A. Marshall et al., Rational design and
cost of materials for manufacturing a small protein engineering of therapeutic proteins, Drug Discov-
can also be an important motivation for reducing the ery Today, 8:212–221, 2003; P. G. Schultz et al., The
size. chemistry of the antibody molecule, Angew. Chem.
To obtain minimalist proteins with novel proper- Int. Ed. Engl., 41:4427–4437, 2002; L. Wang and P. G.
ties, libraries with large numbers of different amino Schultz, Expanding the genetic code, Chem. Com-
acid sequences have been created. These sequences mun., 1:1–11, 2002.
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