Pam3s

Pam3s refers to a class of synthetic lipopeptides designed to mimic bacterial lipoproteins, with Pam3CSK4 being the best-known example. The term often appears in immunology literature as shorthand for triacylated lipopeptides that activate Toll-like receptor 2 (TLR2). The design incorporates an N-terminal palmitoyl group (the “Pam” prefix) linked to a short peptide core, which enables attachment of three lipid chains and engagement with TLR2.

Mechanism of action involves binding of TLR2 in heterodimers with TLR1, triggering MyD88-dependent signaling. This activation leads to downstream pathways such as NF-κB and MAP kinases, resulting in the production of pro-inflammatory cytokines and chemokines (for example TNF-α and IL-6) by participating immune cells. Pam3CSK4 is thus used to study innate immune responses and TLR2 signaling in various cell types.

Applications and use include stimulating monocytes, dendritic cells, and other immune cells in laboratory experiments, probing TLR2-mediated pathways, and serving as a positive control in TLR assays. In vivo use has been explored but is limited by potential inflammatory effects, and Pam3CSK4 is not broadly approved for clinical vaccination.

Variants and related compounds include Pam2CSK4, a diacylated lipopeptide that engages TLR2 in conjunction with TLR6, contrasting with Pam3CSK4’s TLR2/TLR1 interaction. Pam3s as a term is generally tied to this group of synthetic lipoproteins used in immunology research.

See also: Toll-like receptor 2; TLR1; TLR6; lipopeptide adjuvants.