Enhanced nitric oxide production by macrophages treated with a cell-penetrating peptide conjugate

Arfatur Rahman, Macgregor A. Matthews, Cameron J. Nowell, David K. Chalmers, Philip E. Thompson, Sandra E. Nicholson, Nicholas Barlow, Raymond S. Norton

Research output: Contribution to journalArticleResearchpeer-review


The SPRY domain-containing SOCS box protein-2 (SPSB2) plays a critical role in the degradation of inducible nitric oxide synthase (iNOS) in macrophages. In this study, we have conjugated a peptide inhibitor of the iNOS-SPSB2 interaction with a cell-penetrating peptide (CPP) for delivery into macrophages, and confirmed its binding to SPSB2. We have assessed the uptake of a fluorophore-tagged analogue by RAW 264.7 and immortalised bone marrow derived macrophage (iBMDM) cell lines, and shown that the CPP-peptide conjugate enhanced NO production. The findings of this study will be useful in further refinement of CPP-peptide conjugates as leads in the development of new antibiotics that target the host innate immune response.

Original languageEnglish
Article number105763
Number of pages9
JournalBioorganic Chemistry
Publication statusPublished - Jun 2022


  • Cell-penetrating peptide
  • iNOS
  • Macrophage
  • Pathogen killing
  • SPSB

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