A growing body of data suggests that therapies based on Toll-like receptors (TLR) targeting, in particular TLR4, holds promise in curing autoimmune and inflammatory pathologies still lacking specific treatment, included several rare diseases. While TLR4 activators (agonists) have already found successful clinical application as vaccine adjuvants, the use of TLR4 blockers (antagonists) as antisepsis agents or as agents against inflammatory diseases (including arthritis, multiple sclerosis, neuroinflammations) and cancer is still at a preclinical phase of development. This minireview focuses on recent achievements on the development of TLR4 modulators based on lipid A structure simplification, in particular on compounds having disaccharide or monosaccharide structures. As the TLR4 activity of natural TLR4 ligands (lipopolysaccharide, LPS and its biologically active part, the lipid A) depends on both the structure of endotoxin aggregates in solution and on single-molecule interaction with MD-2 and CD14 receptors, the rational design of TLR4 modulators should in principle take into account both these factors. In the light of the most recent advances in the field, in this minireview we discuss the structure-activity relationship in simplified lipid A analogs, with cationic or anionic amphiphilic structures.

Calabrese, V., Cighetti, R., Peri, F. (2015). Molecular simplification of lipid A structure: TLR4-modulating cationic and anionic amphiphiles. MOLECULAR IMMUNOLOGY, 63(2), 153-161 [10.1016/j.molimm.2014.05.011].

Molecular simplification of lipid A structure: TLR4-modulating cationic and anionic amphiphiles

Calabrese V.;Cighetti R.;Peri F.
2015

Abstract

A growing body of data suggests that therapies based on Toll-like receptors (TLR) targeting, in particular TLR4, holds promise in curing autoimmune and inflammatory pathologies still lacking specific treatment, included several rare diseases. While TLR4 activators (agonists) have already found successful clinical application as vaccine adjuvants, the use of TLR4 blockers (antagonists) as antisepsis agents or as agents against inflammatory diseases (including arthritis, multiple sclerosis, neuroinflammations) and cancer is still at a preclinical phase of development. This minireview focuses on recent achievements on the development of TLR4 modulators based on lipid A structure simplification, in particular on compounds having disaccharide or monosaccharide structures. As the TLR4 activity of natural TLR4 ligands (lipopolysaccharide, LPS and its biologically active part, the lipid A) depends on both the structure of endotoxin aggregates in solution and on single-molecule interaction with MD-2 and CD14 receptors, the rational design of TLR4 modulators should in principle take into account both these factors. In the light of the most recent advances in the field, in this minireview we discuss the structure-activity relationship in simplified lipid A analogs, with cationic or anionic amphiphilic structures.
Articolo in rivista - Review Essay
Carbohydrates; Inflammation; Innate immunity; Lipid A; Sepsis; TLR4; Animals; Anions; Cations; Humans; Lipid A; Molecular Conformation; Surface-Active Agents; Toll-Like Receptor 4;
English
2015
63
2
153
161
none
Calabrese, V., Cighetti, R., Peri, F. (2015). Molecular simplification of lipid A structure: TLR4-modulating cationic and anionic amphiphiles. MOLECULAR IMMUNOLOGY, 63(2), 153-161 [10.1016/j.molimm.2014.05.011].
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/269922
Citazioni
  • Scopus 27
  • ???jsp.display-item.citation.isi??? 27
Social impact