Synthetic agonists of NOD-like, RIG-I-like, and C-type lectin receptors for probing the inflammatory immune response

Abstract

Synthetic agonists of innate immune cells are of interest to immunologists due to their synthesis from well-defined materials, optimized activity, and monodisperse chemical purity. These molecules are used in both prophylactic and therapeutic contexts from vaccines to cancer immunotherapies. In this review we highlight synthetic agonists that activate innate immune cells through three classes of pattern recognition receptors: NOD-like receptors, RIG-I-like receptors, and C-type lectin receptors. We classify these agonists by the receptor they activate and present them from a chemical perspective, focusing on structural components that define agonist activity. We anticipate this review will be useful to the medicinal chemist as a guide to chemical motifs that activate each receptor, ultimately illuminating a chemical space ripe for exploration.

Keywords: C-type lectin receptor; NOD-like receptor; RIG-I-like receptor; benzothiazole; cord factor; diaminopimelic acid; glycodendrimer; glycomimetic; isoflavone; mannose; muramyl dipeptide; pattern recognition receptors; poly(I:C); saponin; synthetic immunology; trehalose.