P. Heinonen et al., A SERIES OF ALKOXY)-2-N-METHYL-1,2,3,4-TETRAHYDROISOQUINOLINES - CYSTEINE-REACTIVE MOLECULAR YARDSTICKS FOR PROBING ALPHA(2)-ADRENERGIC RECEPTORS, Bioconjugate chemistry, 9(3), 1998, pp. 358-364
Citations number
14
Categorie Soggetti
Chemistry Inorganic & Nuclear",Biology,"Biochemical Research Methods",Chemistry
A series of alkoxy)-2-N-methyl-1,2,3,4-tetrahydroisoquinolines (7a-d)
was prepared and characterized as SH-reactive molecular yardsticks use
ful in probing az-adrenergic receptors. Rapid displacement of the meth
anesulfonyl group by a cysteine residue in dilute aqueous solution wit
h concomitant formation of a disulfide conjugate was verified by MALDI
-TOF mass spectrometric analysis of the reaction of 7a with a cysteine
-containing decapeptide. 7a-d all showed a marked affinity for the thr
ee different variants of human alpha(2)-adrenergic receptors: H alpha(
2A)wt, H alpha(2B)wt, and mutant H alpha(2A)Ser201Cys197. However, onl
y the mutated receptor (H alpha(2A)Ser201Cys197) was irreversibly inac
tivated, and the extent of inactivation in this case was linearly depe
ndent on the length of the side chain of 7a-d. These results show that
the molecular yardstick approach tested here can provide useful infor
mation for modeling receptor proteins.