Peptidomimetic

A peptidomimetic is a small protein-like chain designed to mimic a peptide. They typically arise from modification of an existing peptide in order to alter the molecule's properties. For example, they may arise from modifications to change the molecule's stability or biological activity. This can have a role in the development of drug-like compounds from existing peptides. These modifications involve changes to the peptide that will not occur naturally (such as altered backbones and the incorporation of nonnatural amino acids).

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An example of peptidomimetics were those designed and synthesized with the purpose of binding to target proteins in order to induce cancer cells into a form of programmed cell death called apoptosis. Basically, these work by mimicking key interactions that activate apoptotic pathway in the cell.

All healthy cells in metazoa (multi-celled animals) are subject to programmed cell death when they are no longer wanted; but cancer cells have the ability to evade apoptosis and the body's attempts to get rid of them. So peptidomimetics are part of the wide effort by researchers, research labs and institutions to create cures for cancer by means of restoring or activating apoptotic pathways in specific cells.

An impressive advance in this effort was reported by Loren D. Walensky and colleagues in the 3 September 2004 issue of the journal Science [1]. This team succeeded in reducing a variety of human leukemic cells that had been xenografted (transplanted) into mice. The peptidomimetic that they succeeded in synthesizing, SAHB (stabilized alpha-helix of BCL-2 domains) specifically activates the mitochondrial apoptotic pathway in the aforementioned malignant cells (see intrinsic and extrinsic inducers of the apoptotic process), without harming healthy tissues.

Lin Li and co-workers reported another impressive advance in the same issue of Science [2]. They were able to synthesize a molecule that mimics the proapoptotic protein called SMAC (whose function is described in biochemical execution of apoptosis).

Further reading

• Denicourt, Catherine, and Dowdy, Steven F.: "Targeting Apoptotic Pathways in Cancer Cells", Science Vol. 305 p. 1411, 3 Sept. 2004 [3].

See also

• Apoptosis
• Cancer
• Beta-peptide
• Foldamers