Redox-stable cyclic peptide inhibitors of the SPSB2-iNOS interaction
- Yap, BK; Harjani, JR; Leung, EW; Nicholson, SE; Scanlon, MJ; Chalmers, DK; Thompson, PE; Baell, JB; Norton, RS;
Publication Year 2016-03, Volume 590 , Issue #6, Page 696-704
- Journal Title
- FEBS Lett
- Publication Type
- Journal Article
- SPSB2 mediates the proteasomal degradation of iNOS. Inhibitors of SPSB2-iNOS interaction are expected to prolong iNO1S lifetime and thereby enhance killing of persistent pathogens. Here, we describe the synthesis and characterization of two redox-stable cyclized peptides containing the DINNN motif required for SPSB2 binding. Both analogues bind with low nanomolar affinity to the iNOS binding site on SPSB, as determined by SPR and 19 F NMR, and efficiently displace full-length iNOS from binding to SPSB2 in macrophage cell lysates. These peptides provide a foundation for future development of redox-stable, potent ligands for SPSB proteins as a potential novel class of anti-infectives. This article is protected by copyright. All rights reserved.
- WEHI Research Division(s)
- PubMed ID
- Publisher's Version
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Creation Date: 2016-03-15 03:47:49Last Modified: 2016-05-09 12:18:58