Speaking today in Barcelona at the Fifth Peptide Engineering Meeting, Compugen Ltd. (NASDAQ:CGEN) project manager Dr. Yossef Kliger provided an overview of Compugen’s DAC Blockers Platform and reviewed disease model data for selected product candidates. Among the product candidates reviewed were targets belonging to the Heat Shock Protein family, currently a key area of focus for Compugen with respect to this platform. A paper describing the DAC Blockers Platform for the in silico design of peptides predicted to block target proteins from attaining disease associated conformations was published in the Proceedings of the National Academy of Sciences USA. 2009 Aug 18; 106(33):13797-801.
Dr. Kliger stated, “Our goal was to design peptides that have the capability to block conformational changes within a target protein, thereby modulating its activity. Towards this goal, Compugen developed a sequence-based computational method for the prediction of intra-molecular interacting alpha helices. We hypothesized that adding peptides corresponding to one of the interacting helices would interfere with the formation of the helix-helix interaction, thereby capturing the target protein in its ‘open’ conformation. To test this hypothesis, Compugen’s scientists synthesized the peptides that were derived from the predicted interacting helices of selected target proteins. The biological function of these peptides was then tested both in vitro and in vivo.”
In his presentation, Dr. Kliger also summarized the results from Compugen’s validation of two of the predicted peptides, each of which was derived from a different stress-induced protein. These two peptides, whose discovery was previously disclosed by Compugen, include: a peptide derived from gp96, a member of the HSP90 family, which was shown to possess anti-inflammatory activities in various animal models; and a peptide derived from clusterin, a versatile chaperone molecule which contains characteristics of small Heat Shock Proteins, which demonstrated positive effects in an animal cancer model.
Dr. Kliger explained, “Heat Shock Proteins are an area of intense interest in the pharmaceutical industry, and the conformational changes that occur concomitant to HSP activation make them optimal targets for the DAC Blockers Platform. Therefore this is an important area of focus for our efforts with this unique platform. Earlier this year, a proteome-wide run of the DAC Blockers Platform resulted in the in silico discovery of a few dozen novel peptides targeting various Heat Shock Proteins in addition to the two previously disclosed product candidates. Several of these peptides are currently undergoing experimental validation. Moreover, in addition to our activities with respect to Heat Shock Proteins, we are also continuing to validate DAC Blocker peptides in other target families of clinical relevance.”
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