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Science

Title:		Genetic selection of peptide inhibitors of biological pathways
Author(s):		Norman TC; Smith DL; Sorger PK; Drees BL; O'Rourke SM; Hughes TR; Roberts CJ; Friend SH; Fields S; Murray AW;
Address:		"Department of Physiology, University of California, San Francisco, CA 94143-0444, USA. tnorman@microbia.com"
Journal Title:		Science
Year:		1999
Volume:		285
Issue:		5427
Page Number:		591 - 595
DOI:		10.1126/science.285.5427.591
ISSN/ISBN:		0036-8075 (Print) 0036-8075 (Linking)
Abstract:		"Genetic selections were used to find peptides that inhibit biological pathways in budding yeast. The peptides were presented inside cells as peptamers, surface loops on a highly expressed and biologically inert carrier protein, a catalytically inactive derivative of staphylococcal nuclease. Peptamers that inhibited the pheromone signaling pathway, transcriptional silencing, and the spindle checkpoint were isolated. Putative targets for the inhibitors were identified by a combination of two-hybrid analysis and genetic dissection of the target pathways. This analysis identified Ydr517w as a component of the spindle checkpoint and reinforced earlier indications that Ste50 has both positive and negative roles in pheromone signaling. Analysis of transcript arrays showed that the peptamers were highly specific in their effects, which suggests that they may be useful reagents in organisms that lack sophisticated genetics as well as for identifying components of existing biological pathways that are potential targets for drug discovery"
Keywords:		Amino Acid Sequence Calcium-Calmodulin-Dependent Protein Kinases/metabolism Fungal Proteins/metabolism G1 Phase Galactose/metabolism Lipoproteins/metabolism Mating Factor Micrococcal Nuclease Mitosis Molecular Sequence Data Peptide Library Peptides/geneti;
Notes:		"MedlineNorman, T C Smith, D L Sorger, P K Drees, B L O'Rourke, S M Hughes, T R Roberts, C J Friend, S H Fields, S Murray, A W eng P41-RR11823/RR/NCRR NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 1999/07/27 Science. 1999 Jul 23; 285(5427):591-5. doi: 10.1126/science.285.5427.591"