WRW4

Chemotactic factors from both Gram-positive and Gram-negative bacteria are short peptides with N-formyl methionine at the N-terminus (extensively reviewed in reference 1). These peptides are released from bacteria during infection and activate formyl peptide receptors (FPR), members of the G-protein coupled receptor (GPCR) superfamily. In humans, the FPR family consists mainly of three receptors, FPR1, FPR2/ALX (formerly FPRL1), and FPR3 (formerly FPRL2) which all couple to the G_i subtype of G-proteins and ultimately lead to the activation of phospholipase C and intracellular Ca²⁺ increase^1,2.

WRW4 is a selective and potent antagonist of the Formyl peptide receptors (FPR2 and FPR3)^3,4, which was identified by screening hexapeptide libraries that inhibit the binding of the FPR2 agonist WKYMVm to its specific receptor, in RBL-2H3 cells³. In human umbilical vein endothelial cells, WRW4 (10 mM), inhibited CCL2 production, which was stimulated by serum amyloid A⁵.

FPR2 is expressed in the promyelocytic leukemia cell line HL-60 as well as in the chronic myelogenous leukemia cell line K562⁶. In human neutrophils, 10 µM WRW4 blocked the specific FPR2 agonist (MMK1) induced Ca²⁺ influx. In addition, at the same concentration WRW4 blocked Ca²⁺ influxes, generated by stimulation with the Alzheimer’s diseases Amiloide β42 peptide, by lipoxin A4 and by fMLF³.