dc.contributor.author |
Kwan, Jason C. |
en |
dc.contributor.author |
Eksioglu, Erika A. |
en |
dc.contributor.author |
Liu, Chen |
en |
dc.contributor.author |
Paul, Valerie J. |
en |
dc.contributor.author |
Luesch, Hendrik |
en |
dc.date.accessioned |
2010-11-18T19:12:50Z |
|
dc.date.available |
2010-11-18T19:12:50Z |
|
dc.date.issued |
2009 |
|
dc.identifier.citation |
Kwan, Jason C., Eksioglu, Erika A., Liu, Chen, Paul, Valerie J., and Luesch, Hendrik. 2009. "<a href="https://repository.si.edu/handle/10088/11223">Grassystatins A-C from Marine Cyanobacteria, Potent Cathepsin E Inhibitors That Reduce Antigen Presentation</a>." <em>Journal of Medicinal Chemistry</em>. 52 (18):5732–5747. <a href="https://doi.org/10.1021/jm9009394">https://doi.org/10.1021/jm9009394</a> |
en |
dc.identifier.issn |
0022-2623 |
|
dc.identifier.uri |
http://hdl.handle.net/10088/11223 |
|
dc.description.abstract |
In our efforts to explore marine cyanobacteria as a source of novel bioactive compounds, we discovered a statine unit-containing linear decadepsipeptide, grassystatin A (1), which we screened against a diverse set of 59 proteases. We describe the structure determination of I and two natural analogues, grassystatins B (2) and C (3), using NMR, MS, and chiral HPLC techniques. Compound I selectively inhibited cathepsins D and E with IC50S of 26.5 nM and 886 pM, respectively. Compound 2 showed similar potency and selectivity against cathepsins D and E (IC50S of 7.27 nM and 354 pM, respectively), whereas the truncated peptide analogue grassystatin C (3), which consists of two fewer residues than I and 2, was less potent against both but still selective for cathepsin E. The selectivity of compounds 1-3 for cathepsin E over D (20-38-fold) suggests that these natural products may be useful tools to probe cathepsin E function. We investigated the structural basis of this selectivity using molecular docking. We also show that I can reduce antigen presentation by dendritic cells, a process thought to rely on cathepsin E. |
en |
dc.relation.ispartof |
Journal of Medicinal Chemistry |
en |
dc.title |
Grassystatins A-C from Marine Cyanobacteria, Potent Cathepsin E Inhibitors That Reduce Antigen Presentation |
en |
dc.type |
Journal Article |
en |
dc.identifier.srbnumber |
80157 |
|
dc.identifier.doi |
10.1021/jm9009394 |
|
rft.jtitle |
Journal of Medicinal Chemistry |
|
rft.volume |
52 |
|
rft.issue |
18 |
|
rft.spage |
5732 |
|
rft.epage |
5747 |
|
dc.description.SIUnit |
NMNH |
en |
dc.description.SIUnit |
NH-SMS |
en |
dc.citation.spage |
5732 |
|
dc.citation.epage |
5747 |
|