Cyclic Peptides Targeting SPSB Proteins as Potential Anti-Infective Agents

Inhibition of the interaction between SPRY domain containing SOCS Box Proteins (SPSB) and inducible nitric oxide synthase (iNOS) increases iNOS levels and cellular NO, and has been proposed to kill intracellular pathogens. Inhibitors of this interaction were discovered previously. However, they cannot penetrate live cells to reach their target proteins. Herein, several potent inhibitors (cyclic peptides and cell penetrating peptide conjugates) were generated. The conjugates were promising in penetrating the cell membrane, although more work need to be done to confirm this. Hence, this study act as a significant step towards the development of SPSB-iNOS inhibitors as potential anti-infective agents