Abstract
BackgroundModern drug discovery is concerned with identification and validation of novel protein targets from among the 30,000 genes or more postulated to be present in the human genome. While protein-protein interactions may be central to many disease indications, it has been difficult to identify new chemical entities capable of regulating these interactions as either agonists or antagonists.ResultsIn this paper, we show that peptide complements (or surrogates) derived from highly diverse random phage display libraries can be used for the identification of the expected natural biological partners for protein and non-protein targets. Our examples include surrogates isolated against both an extracellular secreted protein (TNFβ) and intracellular disease related mRNAs. In each case, surrogates binding to these targets were obtained and found to contain partner information embedded in their amino acid sequences. Furthermore, this information was able to identify the correct biological partners from large human genome databases by rapid and integrated computer based searches.ConclusionsModified versions of these surrogates should provide agents capable of modifying the activity of these targets and enable one to study their involvement in specific biological processes as a means of target validation for downstream drug discovery.
Highlights
Modern drug discovery is concerned with identification and validation of novel protein targets from among the >30,000 genes postulated to be present in the human genome [1]
We examine each peptide for significant differences in the expected frequency of amino acids and the number of times a specific peptide sequence has been repeated
Homology between the partner and surrogate oftentimes ranges over a long stretch (15–20 amino acids) or may be found in a perfect match within a short sequence of 5–8 amino acids
Summary
Modern drug discovery is concerned with identification and validation of novel protein targets from among the 30,000 genes or more postulated to be present in the human genome. In understanding the importance of any new gene and its connection to a given phenotype, there is the need to know the immediate "neighborhood" of partners for each gene product since they are most likely involved in the action of the gene product In this regard, there are few if any new chemical entities (NCEs) capable of regulating protein:protein interactions as either agonists or antagonists. BMC Biotechnology 2001, 1:6 http://www.biomedcentral.com/1472-6750/1/6 used to obtain information about protein:protein interactions as well as regulate their activity [2,3] This has most often been accomplished with libraries consisting of peptides between
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
