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Genetic selection of peptide aptamers that recognize and inhibit cyclin-dependent kinase 2

Nature volume 380, pages 548–550 (1996)Cite this article

Abstract

A NETWORK of interacting proteins controls the activity of cyclin-dependent kinase 2 (Cdk2) (refs 1, 2) and governs the entry of higher eukaryotic cells into S phase. Analysis of this and other genetic regulatory networks would be facilitated by intracellular reagents that recognize specific targets and inhibit specific network connections. We report here the expression of a combinatorial library of constrained 20-residue peptides displayed by the active-site loop of Escherichia coli thioredoxin, and the use of a two-hybrid system to select those that bind human Cdk2. These peptide aptamers were designed to mimic the recognition function of the complementarity-determining regions of immuno-globulins. The aptamers recognized different epitopes on the Cdk2 surface with equilibrium dissociation constant in the nanomolar range; those tested inhibited Cdk2 activity. Our results show that peptide aptamers bear some analogies with monoclonal antibodies, with the advantages that they are isolated together with their coding genes, that their small size should allow their structures to be solved, and that they are designated to function inside cells.

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Author notes

  1. Timm Jessen

    Present address: Hoechst Marion Roussel, Building H825, D-65926, Frankfurt, Germany

  2. John McCoy: Genetics Institute Inc., 89 Cambridge Park Drive, Cambridge, Massachusetts 02142, USA

Authors and Affiliations

  1. Department of Molecular Biology, Massachusetts General Hospital, 50 Blossom Street, Boston, Massachusetts, 02114

    Pierre Colas, Barak Cohen, Timm Jessen, Irina Grishina, John McCoy & Roger Brent

  2. Department of Genetics, Harvard Medical School, Boston, Massachusetts, 02115, USA

    Pierre Colas, Barak Cohen, Timm Jessen, Irina Grishina, John McCoy & Roger Brent

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  1. Pierre Colas
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  4. Irina Grishina
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  5. John McCoy
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  6. Roger Brent
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Colas, P., Cohen, B., Jessen, T. et al. Genetic selection of peptide aptamers that recognize and inhibit cyclin-dependent kinase 2. Nature 380, 548–550 (1996). https://doi.org/10.1038/380548a0

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