re. NBSC...........
BMC Biotechnol 2001;1(1):6
A surrogate-based approach for post-genomic partner identification.
Pillutla RC, Hsiao Kc K, Brissette R, Eder PS, Giordano T, Fletcher PW, Lennick M,
Blume AJ, Goldstein NI.
DGI BioTechnologies, Inc, Edison NJ, USA. goldstein@dgibt.com
BACKGROUND: 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. 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. RESULTS: In 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 (TNFbeta)
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. CONCLUSIONS:
Modified 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.
link to the entire manuscript.............
biomedcentral.com |
