>> 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. |
