Auto-inducing peptides

The discovery of a global regulatory system for virulence in S. aureus, mediated by small auto-inducing peptides (AlPs) has opened a new avenue to the interruption of microbial defences, and consequently, to overcoming resistance to many antibiotics. Microbial defensive mechanisms, based on mutation, drug efflux pathways, biofilm formation and the secretion of virulence factors, have become the major threat to modem antibiotic therapy. 

Fig. 12.2 Schematic representation of auto-inducing peptides AIP I-IV from S. aureus species...

As mentioned in the introduction to this chapter, the recent discovery of thiolactone peptides as potential antimicrobial agents, based on flieir ability to act as antagonists of natural auto-inducing peptides (AIP), prompted the new synthetic achievements, which permitted the synthesis of these cyclic peptide inhibitors. Here, we discuss the most recent achievement in the synthesis of AIP mimics, based on an original linker for the Fmoc-based solid-phase methodology. 

World Pat. 9529700-A1 (1995), B. F. Haynes and T. J. Palker, "New Peptide Corresponding to HIV Sequences Used for Inducing Protective Immunity to HIV and in the Treatment of e.g. Auto-Immune Disease Infectious Diseases and Tumors" (to Duke University). 

A toxin or one of its metabolites may bind to an (auto)-antigen (Figure 2A). The complex will be internalized and processed by antigen presenting cells. The peptide modified by the toxin will activate specific T-cells. This mechanism was referred to as underlying minocyclin-induced vasculitis with ANCA [44]. 

These intervention strategies can be considered as passive immunotherapy it may, however, be possible to actively immunize atopic individuals since there is evidence that neonatal or adult immunization with IgE can stimulate the formation of therapeutically useful anti-IgE auto-antibodies in animal systems (342). Their action suggests that the identification of structural determinants in IgE, which participate directly in IgE-receptor interaction, may form the basis for the development of peptide immunogens to induce the formation of antibodies, which can bind specifically to the receptor-binding sites of IgE in the circulation and to membrane IgE on B cells. Used as vaccines, such peptides could have a direct application in the treatment of all IgE-mediated allergies. 

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