Chemistry

A Cyclic Inhibitor of Cycling

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Science  01 Oct 2004:
Vol. 306, Issue 5693, pp. 23
DOI: 10.1126/science.306.5693.23a

The introduction of structural constraints into flexible molecules is often used in medicinal chemistry to improve the affinity of the molecules to their target. Andrews et al. have used this approach to design cyclic peptide inhibitors for cyclin-dependent kinase 2 (CDK2), a potential target for intervention in cancer and other proliferative diseases. They based their peptides on the Leu-Phe-Gly cyclin groove recognition motif in the tumor suppressor protein p27KIP1. A covalent link between a side chain and the tail of the peptide mimicks an intramolecular hydrogen bond in the CDK2/cyclin A/p27KIP1 crystal structure. The resulting cyclic compounds showed increased potency as compared with their linear counterparts. — JFU

Org. Biomol. Chem. 2, 10.1039/b409157d (2004).

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