| pubmed-article:15572368 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15572368 | lifeskim:mentions | umls-concept:C0021080 | lld:lifeskim |
| pubmed-article:15572368 | lifeskim:mentions | umls-concept:C0010592 | lld:lifeskim |
| pubmed-article:15572368 | lifeskim:mentions | umls-concept:C0021079 | lld:lifeskim |
| pubmed-article:15572368 | lifeskim:mentions | umls-concept:C1280500 | lld:lifeskim |
| pubmed-article:15572368 | lifeskim:mentions | umls-concept:C1524075 | lld:lifeskim |
| pubmed-article:15572368 | lifeskim:mentions | umls-concept:C1709915 | lld:lifeskim |
| pubmed-article:15572368 | lifeskim:mentions | umls-concept:C0243072 | lld:lifeskim |
| pubmed-article:15572368 | lifeskim:mentions | umls-concept:C0337112 | lld:lifeskim |
| pubmed-article:15572368 | pubmed:issue | 6 | lld:pubmed |
| pubmed-article:15572368 | pubmed:dateCreated | 2005-2-7 | lld:pubmed |
| pubmed-article:15572368 | pubmed:abstractText | To dissect the enzyme inhibitory properties of the immunosuppressive cyclic undecapeptide cyclosporin A (CsA) and gain access to monospecific, non-calcineurin-inhibiting CsA derivatives, [D-Ser8]CsA was subjected to modifications at the D-Ser side chain. Thus, we modified a CsA residue flanking the calcineurin (CaN) and cyclophilin 18 (Cyp18) binding domains of CsA instead of the residues of the CaN binding domain in order to develop a new specificity-determining site within the cyclic peptide. The [O-(NH2 (CH2)5NHC(O)CH2)-D-Ser8]CsA (derivative 9), with an amino group on a tether, exhibits CsA-like inhibition of the peptidyl prolyl cis/trans isomerase activity of Cyp18 with an IC50 value of 3.2 nm, whereas the CaN inhibition by the Cyp18-derivative 9 complex is completely abolished. Consequently, this compound is not able to inhibit the proliferation and cytokine production of activated T cells. Structure-activity relationship studies with a series of [d-Ser(8)]CsA derivatives indicate that the positively charged side chain is an essential requirement for Cyp18-derivative 9 to be ineffective on CaN. Upon protecting the amino group in derivative 9 with the photolabile moiety 2-nitroveratryloxycarbonyl (NVOC), the Cyp18-[O-(NVOC-NH(CH2)5NHC(O)CH2)-D-Ser8]CsA (derivative 11) complex exhibits strong CaN inhibition and shows potent immunosuppressive activity. In stimulated T cells pretreated with derivative 11, a remarkable recovery of transcriptional activation of the nuclear factor of activated T cells (NFAT) has been achieved through light irradiation, as assessed with a NFAT reporter gene assay. | lld:pubmed |
| pubmed-article:15572368 | pubmed:language | eng | lld:pubmed |
| pubmed-article:15572368 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15572368 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:15572368 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:15572368 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15572368 | pubmed:month | Feb | lld:pubmed |
| pubmed-article:15572368 | pubmed:issn | 0021-9258 | lld:pubmed |
| pubmed-article:15572368 | pubmed:author | pubmed-author:FischerGunter... | lld:pubmed |
| pubmed-article:15572368 | pubmed:author | pubmed-author:SchutkowskiMi... | lld:pubmed |
| pubmed-article:15572368 | pubmed:author | pubmed-author:ZhangYixinY | lld:pubmed |
| pubmed-article:15572368 | pubmed:author | pubmed-author:BaumgrassRiaR | lld:pubmed |
| pubmed-article:15572368 | pubmed:author | pubmed-author:ErdmannFrankF | lld:pubmed |
| pubmed-article:15572368 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:15572368 | pubmed:day | 11 | lld:pubmed |
| pubmed-article:15572368 | pubmed:volume | 280 | lld:pubmed |
| pubmed-article:15572368 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15572368 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15572368 | pubmed:pagination | 4842-50 | lld:pubmed |
| pubmed-article:15572368 | pubmed:dateRevised | 2008-11-21 | lld:pubmed |
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| pubmed-article:15572368 | pubmed:year | 2005 | lld:pubmed |
| pubmed-article:15572368 | pubmed:articleTitle | Unexpected side chain effects at residue 8 of cyclosporin a derivatives allow photoswitching of immunosuppression. | lld:pubmed |
| pubmed-article:15572368 | pubmed:affiliation | Max Planck Research Unit for Enzymology of Protein Folding, Weinbergweg 22, D-06120, Halle/Saale, Germany. | lld:pubmed |
| pubmed-article:15572368 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:15572368 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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