A Series of 6-(-Methanesulfonylthioalkoxy)-2-N-methyl- 1,2,3,4-tetrahydroisoquinolines: Cysteine-Reactive Molecular Yardstick
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- 作者：Petri Heinonen ; Katja Koskua ; Marjo Pihlavisto ; Anne Marjamä ; ki ; Victor Cockcroft ; Juha-Matti Savola ; Mika Scheinin ; and Harri Lö ; nnberg
- 刊名：Bioconjugate Chemistry
- 出版年：1998
- 出版时间：May 1998
- 年：1998
- 卷：9
- 期：3
- 页码：358 - 364
- 全文大小：92K
- 年卷期：v.9,no.3(May 1998)
- ISSN：1520-4812
文摘
A series of6-(
-methanesulfonylthioalkoxy)-2-N-methyl-1,2,3,4-tetrahydroisoquinolines(7a-d) wasprepared and characterized as SH-reactive molecular yardsticks usefulin probing 
2-adrenergicreceptors. Rapid displacement of the methanesulfonyl group by acysteine residue in dilute aqueoussolution with concomitant formation of a disulfide conjugate wasverified by MALDI-TOF massspectrometric analysis of the reaction of 7a with acysteine-containing decapeptide.7a-d all showeda marked affinity for the three different variants of human2-adrenergic receptors: H2Awt,H2Bwt, and mutant H2ASer201Cys197. However, onlythe mutated receptor (H2ASer201Cys197)wasirreversibly inactivated, and the extent of inactivation in this casewas linearly dependent on thelength of the side chain of 7a-d.These results show that the molecular yardstick approachtestedhere can provide useful information for modeling receptorproteins.
-methanesulfonylthioalkoxy)-2-N-methyl-1,2,3,4-tetrahydroisoquinolines(7a-d) wasprepared and characterized as SH-reactive molecular yardsticks usefulin probing 2-adrenergicreceptors. Rapid displacement of the methanesulfonyl group by acysteine residue in dilute aqueoussolution with concomitant formation of a disulfide conjugate wasverified by MALDI-TOF massspectrometric analysis of the reaction of 7a with acysteine-containing decapeptide.7a-d all showeda marked affinity for the three different variants of human2-adrenergic receptors: H2Awt,H2Bwt, and mutant H2ASer201Cys197. However, onlythe mutated receptor (H2ASer201Cys197)wasirreversibly inactivated, and the extent of inactivation in this casewas linearly dependent on thelength of the side chain of 7a-d.These results show that the molecular yardstick approachtestedhere can provide useful information for modeling receptorproteins.