Toll-like Receptor Inhibitors: Small Molecules and Peptides

TLRs make up a family of pattern recognition receptors that play important roles in the innate immune response. Broad classes of pathogens (e.g. viruses, bacteria, and fungi) constitutively express a set of mutation-resistant molecules called pathogen-associated molecular patterns (PAMPs). These microbial molecular markers may be composed of proteins, carbohydrates, lipids, nucleic acids and/or combinations thereof. Individual TLRs recognize distinct pathogen-associated PAMPs, initiating signaling cascades that promote the immune response. Structurally, TLRs are type I transmembrane receptors that possess varying numbers of extracellular N-terminal leucine-rich repeat (LRR) motifs, followed by a cysteine-rich region, a TM domain, and an intracellular Toll/IL-1 R (TIR) motif. The TIR motif is common to the larger IL-1 R/TLR superfamily.