Compugen identifies new peptide ligands

GPCRs are membrane protein receptors that are involved in signal transduction of numerous physiological processes. GPCRs are by far the largest family of known drug targets, and at least 40% of drugs currently available are thought to act on GPCRs. Furthermore, newly discovered GPCR peptide ligands have in the past shown a high probability of being successfully developed into new drugs.

The discovery engine used by Compugen in making these discoveries incorporates a proprietary model of the “peptidome”, an in silico prediction of probable human peptides. Peptides are formed through the cleavage of precursor proteins, and Compugen’s proprietary peptidome – already consisting of thousands of novel human peptide sequences – is based on predicting cleavage sites in precursor proteins.

The discovery engine uses proprietary machine-learning algorithms to analyze the predictive peptidome and to date has identified hundreds of peptides likely to activate GPCRs. Thirty three of these peptides, all novel, have been synthesized and screened in a functional assay against a panel of 152 GPCRs. Eight peptides were shown to activate six different GPCRs in a concentration-dependent manner, including some for which there are no known endogenous ligands.

The receptors for which novel ligands have been discovered include the MAS1 and MAS-related GPCRs, MRGX1 and MRGX2, as well as FPRL1 and two of the Relaxin family receptors, RXFP1 and RXFP2.

“Out of the eight ligands already discovered, we have selected two for further development at Compugen,” commented said Dr Yossi Cohen, vice president of R&D, Compugen Ltd. “Others are undergoing an evaluation process both for in-house development and for out-licensing opportunities.”