200010-31-7

Upstream product

• 1435932-57-2 C₄₀H₆₄N₁₀O₁₂S₂ 

Relevant academic research and scientific papers

Structure-activity relationship study based on autoinducing peptide (AIP) from dog pathogen S. schleiferi

Herein, an effective protocol for solid-phase synthesis of peptide thiolactones by concomitant ring closure and cleavage from the solid support is reported. The strategy was applied for mapping the importance of the structural features in S. schleiferi AIP (5) by performing an alanine scan and truncation of this natural compound. This furnished some of the most potent inhibitors of accessory gene regulator (agr)-I in the human pathogen S. aureus reported to date.

Identification of autoinducing thiodepsipeptides from staphylococci enabled by native chemical ligation

Staphylococci secrete autoinducing peptides (AIPs) as signalling molecules to regulate population-wide behaviour. AIPs from non-Staphylococcusaureus staphylococci have received attention as potential antivirulence agents to inhibit quorum sensing and viru

Peptide-based quorum sensing inhibitors for the attenuation of virulence in Staphylococcus aureus

Compounds that affect quorum sensing (QS) in Staphylococcus aureus and related Staphylococcus species (e.g., S. epidermidis). Compounds which modulate one or more of the four AgrC receptors of Staphylococcus species, particularly of Staphylococcus aureus.

Highly potent inhibitors of quorum sensing in staphylococcus aureus revealed through a systematic synthetic study of the group-III autoinducing peptide

Methods to intercept bacterial quorum sensing (QS) have attracted significant attention as potential anti-infective therapies. Staphylococcus aureus is a major human pathogen that utilizes autoinducing peptide (AIP) signals to mediate QS and thereby regulate virulence. S. aureus strains are categorized into four groups (I-IV) according to their AIP signal and cognate extracellular receptor, AgrC. Each group is associated with a certain disease profile, and S. aureus group-III strains are responsible for toxic shock syndrome and have been underestimated in other infections to date. A limited set of non-native AIP analogs have been shown to inhibit AgrC receptors; such compounds represent promising tools to study QS pathways in S. aureus. We seek to expand this set of chemical probes and report herein the first design, synthesis, and biological testing of AIP-III mimetics. A set of non-native peptides was identified that can inhibit all four of the AgrC receptors (I-IV) with picomolar IC50 values in reporter strains. These analogs also blocked hemolysis by wild-type S. aureus group I-IV strains - a virulence trait under the control of QS - at picomolar concentrations. Moreover, four of the lead AgrC inhibitors were capable of attenuating the production of toxic shock syndrome toxin-1 (also under the control of QS) by over 80% at nanomolar concentrations in a wild-type S. aureus group-III strain. These peptides represent, to our knowledge, the most potent synthetic inhibitors of QS in S. aureus known, and constitute new and readily accessible chemical tools for the study of the AgrC system and virulence in this deadly pathogen.