A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
A series of 6-(omega-methanesulfonylthioalkoxy)-2-N-methyl-1,2,3,4-tetrahydroisoquinolines: Cysteine-reactive molecular yardsticks for probing alpha(2)-adrenergic receptors
Tekijät: Heinonen P, Koskua K, Pihlavisto M, Marjamaki A, Cockcroft V, Savola JM, Scheinin M, Lonnberg H
Kustantaja: AMER CHEMICAL SOC
Julkaisuvuosi: 1998
Lehti:: Bioconjugate Chemistry
Tietokannassa oleva lehden nimi: BIOCONJUGATE CHEMISTRY
Lehden akronyymi: BIOCONJUGATE CHEM
Vuosikerta: 9
Numero: 3
Aloitussivu: 358
Lopetussivu: 364
Sivujen määrä: 7
ISSN: 1043-1802
DOI: https://doi.org/10.1021/bc970193o
Tiivistelmä
A series of 6-(omega-methanesulfonylthioalkoxy)-2-N-methyl-1,2,3,4-tetrahydroisoquinolines (7a-d) was prepared and characterized as SH-reactive molecular yardsticks useful in probing az-adrenergic receptors. Rapid displacement of the methanesulfonyl group by a cysteine residue in dilute aqueous solution with 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 three different variants of human alpha(2)-adrenergic receptors: H alpha(2A)wt, H alpha(2B)wt, and mutant H alpha(2A)Ser201Cys197. However, only the mutated receptor (H alpha(2A)Ser201Cys197) was irreversibly inactivated, and the extent of inactivation in this case was linearly dependent on the length of the side chain of 7a-d. These results show that the molecular yardstick approach tested here can provide useful information for modeling receptor proteins.
A series of 6-(omega-methanesulfonylthioalkoxy)-2-N-methyl-1,2,3,4-tetrahydroisoquinolines (7a-d) was prepared and characterized as SH-reactive molecular yardsticks useful in probing az-adrenergic receptors. Rapid displacement of the methanesulfonyl group by a cysteine residue in dilute aqueous solution with 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 three different variants of human alpha(2)-adrenergic receptors: H alpha(2A)wt, H alpha(2B)wt, and mutant H alpha(2A)Ser201Cys197. However, only the mutated receptor (H alpha(2A)Ser201Cys197) was irreversibly inactivated, and the extent of inactivation in this case was linearly dependent on the length of the side chain of 7a-d. These results show that the molecular yardstick approach tested here can provide useful information for modeling receptor proteins.
Turun yliopiston Tutkimustietojärjestelmän portaali