MMK1

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.

MMK1 is a selective and potent agonist of the Formyl peptide receptor FPR2³, which was originally derived from a random peptide library and was identified by a novel autocrine selection method in yeast engineered to express human FPR2⁴.

FPR2 is expressed in the promyelocytic leukemia cell line HL-60 as well as in the chronic myelogenous leukemia cell line K562⁵. In human neutrophils, 1 µM MMK1 induces Ca²⁺ influx which is blocked by the specific FPR2 antagonist WRW4⁶.

Resveratrol, a constituent of grape seeds, induces Ca²⁺ influx in human monocytes which is blocked by 10 µM MMK1, demonstrating that the inhibition of chemoattractant receptors contribute to the anti-inflammatory properties of resveratrol⁷.