Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-1-13
pubmed:abstractText
Complement factor C5a is one of the most powerful pro-inflammatory agents involved in recruitment of leukocytes, activation of phagocytes and other inflammatory responses. C5a triggers inflammatory responses by binding to its G-protein-coupled C5a-receptor (C5aR). Excessive or erroneous activation of the C5aR has been implicated in numerous inflammatory diseases. The C5aR is therefore a key target in the development of specific anti-inflammatory compounds. A very potent natural inhibitor of the C5aR is the 121-residue chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS). Although CHIPS effectively blocks C5aR activation by binding tightly to its extra-cellular N terminus, it is not suitable as a potential anti-inflammatory drug due to its immunogenic properties. As a first step in the development of an improved CHIPS mimic, we designed and synthesized a substantially shorter 50-residue adapted peptide, designated CHOPS. This peptide included all residues important for receptor binding as based on the recent structure of CHIPS in complex with the C5aR N terminus. Using isothermal titration calorimetry we demonstrate that CHOPS has micromolar affinity for a model peptide comprising residues 7-28 of the C5aR N terminus including two O-sulfated tyrosine residues at positions 11 and 14. CD and NMR spectroscopy showed that CHOPS is unstructured free in solution. Upon addition of the doubly sulfated model peptide, however, the NMR and CD spectra reveal the formation of structural elements in CHOPS reminiscent of native CHIPS.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/20683629-10992501, http://linkedlifedata.com/resource/pubmed/commentcorrection/20683629-11062244, http://linkedlifedata.com/resource/pubmed/commentcorrection/20683629-11342590, http://linkedlifedata.com/resource/pubmed/commentcorrection/20683629-15153520, http://linkedlifedata.com/resource/pubmed/commentcorrection/20683629-15452845, http://linkedlifedata.com/resource/pubmed/commentcorrection/20683629-15542591, http://linkedlifedata.com/resource/pubmed/commentcorrection/20683629-15638737, http://linkedlifedata.com/resource/pubmed/commentcorrection/20683629-15771587, http://linkedlifedata.com/resource/pubmed/commentcorrection/20683629-16213522, http://linkedlifedata.com/resource/pubmed/commentcorrection/20683629-17258808, http://linkedlifedata.com/resource/pubmed/commentcorrection/20683629-17603557, http://linkedlifedata.com/resource/pubmed/commentcorrection/20683629-19251703, http://linkedlifedata.com/resource/pubmed/commentcorrection/20683629-20004096, http://linkedlifedata.com/resource/pubmed/commentcorrection/20683629-8417126, http://linkedlifedata.com/resource/pubmed/commentcorrection/20683629-9519303, http://linkedlifedata.com/resource/pubmed/commentcorrection/20683629-9553099
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1438-2199
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
731-40
pubmed:dateRevised
2011-7-25
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
A peptide mimic of the chemotaxis inhibitory protein of Staphylococcus aureus: towards the development of novel anti-inflammatory compounds.
pubmed:affiliation
Department of Medicinal Chemistry and Chemical Biology, Utrecht University, Sorbonnelaan 16, 3584 CA, Utrecht, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't