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Biotech / Medical : Tularik Inc. (TLRK) -- Ignore unavailable to you. Want to Upgrade?

To: tommysdad who wrote (72)	9/14/2000 1:15:54 AM
From: scaram(o)uche	Read Replies (3) \| Respond to of 598

Arena and 3-Dimensional Pharm. There's also OSIP and KDUS, but that's more of a focus on high throughput GPCR-directed screening of libraries. The way to go here, as far as I'm concerned, if to focus on "phenotyping companies" like LEXG, while you're studying these high throughput efforts to assign function from in vitro screens. If someone has already done the studying, please speak up! -- I'm confused. A couple of friends have been looking at an Arena report from Toth, but I haven't had the time to look at their comments. The KDUS system is still available. You can buy the entire company for $16M if you can wrest the shares out of my hands and others at the current price. Feed the 50 GPCRs that are co-owned with GENE into knockouts? OSI obviously knows that the KDUS screen for non-receptor modulators (Cismowski et al.) works. But that's not what SNAP is talking about..... they're talking about assigning function to the GPCRs. We need someone from SNAP, OSIP and ARNA to sit down and give a day-long seminar, starting from the very basics. Someone, somewhere, must have all of this stuff clearly tucked away. I just don't get what SNAP is talking about.... it still sounds like hit and miss to me, assigning function to the gene, even though they have engineered a read-out into mammalian cells. Does that make sense? For those that might want to venture into clarification, here's the abstract describing the basic KDUS system...... Nat Biotechnol 1998 Dec;16(13):1334-7 Related Articles, Books Identification of surrogate agonists for the human FPRL-1 receptor by autocrine selection in yeast. Klein C, Paul JI, Sauve K, Schmidt MM, Arcangeli L, Ransom J, Trueheart J, Manfredi JP, Broach JR, Murphy AJ Cadus Pharmaceutical Corporation, Tarrytown, NY 10591-6705, USA. christine.klein@cadus.com We describe a procedure for isolating agonists for mammalian G protein-coupled receptors of unknown function. Human formyl peptide receptor like-1 (FPRL-1) receptor, originally identified as an orphan G protein-coupled receptor related to the formyl peptide receptor (FPR1), was expressed in Saccharomyces cells designed to couple receptor activation to histidine prototrophy. Selection for histidine prototrophs among transformants obtained with a plasmid-based library encoding random peptides identified six different agonists, each of whose production yielded autocrine stimulation of the receptor expressed in yeast. A synthetic version of each peptide promoted activation of FPRL-1 expressed in human embryonic kidney (HEK293) cells, and five of the peptides exhibited significant selectivity for activation of FPRL-1 relative to FPR1. One selective peptide was tested and found to mobilize calcium in isolated human neutrophils. This demonstrates that stimulation of FPRL-1 results in neutrophil activation and suggests that the receptor functions as a component of the inflammatory response. This autocrine selection protocol may be a generally applicable method for providing pharmacological tools to evaluate the physiological roles of the growing number of mammalian orphan G protein-coupled receptors.