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Biotech / Medical : ACADIA Pharmaceuticals Inc (ACAD) -- Ignore unavailable to you. Want to Upgrade?

To: tuck who wrote (141)	7/6/2005 12:25:34 PM
From: scaram(o)uche	Read Replies (1) \| Respond to of 588

>> Nice dig, Rick, on the FPRL1 patent application << You may get a kick outta this........ Message 18543176 Message 19296865 Nat Biotechnol 1998 Dec;16(13):1334-7 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.