Linked Life Data

3712387

Source:http://linkedlifedata.com/resource/pubmed/id/3712387

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1986-7-7
pubmed:abstractText
Cyclosporin A (CSA, 1), an immunosuppressive cyclic undecapeptide, contains a unique N-methylated amino acid, (2S,3R,4R,6E)-3-hydroxy-4-methyl-2-(N-methylamino)-6-octenoic++ + acid, called both C-9-ene and MeBmt [(4R)-N-methyl-4-butenyl-4-methylthreonine] that may be essential for the biological activity of CSA. In order to determine the minimal portion of MeBmt needed for antimitogenic activity, four analogues of CSA specifically modified in the 1-position have been synthesized. These are (MeThr1)CSA (4), (MeAbu1)CSA (5), (MeAbu1,Sar10)CSA (6), and [(MeLeu(3-OH)1)]CSA (7). The synthesis of analogues was carried out by forming a linear undecapeptide that was cyclized at the two non-N-methylated amino acids. The structure of cyclic analogues 4-7 and their corresponding precursors were established unequivocally by 1H NMR, FAB mass spectrometry, elemental analysis, and HPLC. The inhibition of Con A stimulated thymocytes by CSA (1), DH-CSA (2), 7, 4, 5, and 6 gave IC50's (nM) of 4, 10, 600, 8 X 10(3), 15 X 10(3), and 40 X 10(3), respectively. The increase in IC50 by modification of the side chain in MeBmt suggested the importance of this amino acid in the 1-position of CSA for full antimitogenic activity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
978-84
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1986
pubmed:articleTitle
Synthesis and antimitogenic activities of four analogues of cyclosporin A modified in the 1-position.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.