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Structural requirements for the modulatory effect of 6-substituted pterins on interleukin 2 receptor binding.

Biochim. Biophys. Acta 1135, 330-334 (1992)
Open Access Green as soon as Postprint is submitted to ZB.
(6R)-5,6,7,8-Tetrahydrobiopterin is produced by stimulated human T lymphocytes, and is known to affect various aspects of interleukin-2-directed T cell proliferation. Using an increased apparent affinity of interleukin 2 receptor to interleukin 2 as a measure of activity, this study explores whether other 6-substituted pterins might have the same effect, and what structural features are necessary for activity. Of the compounds tested, only the T-lymphocyte-derived (6R)-5,6,7,8-tetrahydrobiopterin was active. The diastereomeric (6S)-5,6,7,8-tetrahydrobiopterin was inactive, as were 7,8-dihydrobiopterin, sepiapterin, 5,6,7,8-tetrahydroneopterin, 6,7-dimethyl-5,6,7,8-tetrahydropterin and 6-hydroxymethylpterin. 7,8-Dihydroneopterin and neopterin were also found to be inactive. It follows that neither of these compounds participates in the feedback modulation of IL-2 receptor affinity, although both of them can be detected upon IFN-γ stimulation of human monocytes/macrophages. A computer-based molecular modelling study of (6R)-5,6,7,8-tetrahydrobiopterin and (6R)-5,6,7,8-tetrahydroneopterin revealed substantial differences in overall shape between the two molecules, with certain features figuring prominently in the low-energy conformers of (6R)-5,6,7,8-tetrahydrobiopterin.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Conformational Analysis ; Interleukin 2 Receptor ; Molecular Modelling ; Neopterin ; Pterin ; Tetrahydrobiopterin
ISSN (print) / ISBN 0006-3002
Quellenangaben Volume: 1135, Issue: 3, Pages: 330-334 Article Number: , Supplement: ,
Publisher Elsevier