Abstract
Anginex, a designed peptide 33mer, is known to function both as an antiangiogenic and bactericidal agent. Solving the NMR solution structure of the peptide is key to understand better its structure-activity relationships and to design more bioactive peptides and peptide mimetics. However, structure elucidation of anginex has been elusive due to subunit exchange-induced resonance broadening. Here, we found that performing NMR structural studies in a micellar environment abolishes exchange broadening and allows the structure of anginex to be determined. Anginex folds in an amphipathic, three-stranded antiparallel β-sheet conformation with functionally key hydrophobic residues lying on one face of the β-sheet and positively charged, mostly lysine residues, lying on the opposite face. Structural comparison is made with a homologous, yet relatively inactive peptide, βpep-28. These results contribute to the design of peptidomimetics of anginex for therapeutic use against angiogenically-related diseases like cancer, as well as infectious diseases.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 645-651 |
| Number of pages | 7 |
| Journal | Biochimica et Biophysica Acta - Proteins and Proteomics |
| Volume | 1774 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2007 |
Bibliographical note
Funding Information:This work was supported by support from the National Institutes of Health (NIH CA-96090 and AI-057153). NMR instrumentation was provided with funds from the NSF (BIR-961477) and the University of Minnesota Medical School. Peptides were synthesized at the Microchemical Facility, University of Minnesota.
Keywords
- Anti-angiogenic
- Anti-bacterial
- Conformation
- Drug design
