Background: Inducible Nitric Oxide Synthase (iNOS or NOS2) produces Nitric Oxide
(NO) and related reactive nitrogen species, which are critical effectors of the host innate response
and play key roles in the intracellular killing of bacterial and parasitic pathogens. The SPRY domain-
containing SOCS box proteins SPSB1 and SPSB2 are key physiological regulators of this
important enzyme. Disrupting the endogenous SPSB-iNOS interaction should prolong the intracellular
lifetime of iNOS and enhance the production of NO, and therefore be beneficial in treating
chronic and persistent infections such as tuberculosis. By using structure-based design, potent peptide
inhibitors of this interaction have been developed.
Conclusion: Inhibitors of the SPSB-iNOS interaction have therapeutic potential as a novel class of
anti-infective agents. Various strategies are being pursued to target these peptide inhibitors to
macrophages and deliver them to the cytoplasm of these cells. It will then be possible to assess the
efficacy of such inhibitors in boosting the capacity of macrophages to destroy infectious pathogens.
Keywords: Nitric oxide, peptide, structure, protein-protein interaction, pathogen, targeting, macrophage, delivery.
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