Naslov
Mechanism of oxime reactivation of phosphorylated acetylcholinesterase analyzed by chirality and mutagenesis

Autori
Radić, Zoran ; Kovarik, Zrinka ; Wong, Lilly ; Bruggemann, Roger J. ; Hosea, Natalie ; Berman, Harvey A. ; Taylor, Palmer

Vrsta, podvrsta i kategorija rada
Radovi u zbornicima skupova, cjeloviti rad (in extenso), znanstveni

Izvornik
US Army Medical Defense BioScience Review 2000 Proceedings, Baltimore, SAD / BP Doctor - Washington (MD) : US Army Medical Research and Materiel Command, 2000, 56-65

Skup
US Army Medical Defense BioScience Review 2000, Baltimore, SAD

Mjesto i datum
Baltimore (MD), Sjedinjene Američke Države, 04.06.2000. - 07.06.2000

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
acetylcholinesterase; organophosphates; reactivation; oximes; chirality

Sažetak
We have examined the reactivation of a series of resolved enantiomeric methylphosphonate conjugates of acetylcholinesterase by two oximes, 2-PAM and HI-6. The rates of oxime reactivation show an Sp versus Rp preferance, similar to that found as previously for inactivation. A comparison of Sp and Rp-cycloheptyl-, 3,3-dimethylbutyl- and isopropyl methylphosphonyl conjugates shows that steric hidrance by the alkoxy group precludes facile access of the oxime to the tetraedral phosphorus. To facilitate access, we substituted smaller side chains in the acyl pocket and choline binding site of the enzyme. Phe295Leu and Phe297Ile acyl pocket substitutions enhance respectively HI-6 and 2-PAM elicited reactivation rates of the Sp conjugates, while in choline binding site Tyr337Ala enhance reactivation rates of both, Sp and Rp, conjugates.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Kliničke medicinske znanosti

POVEZANOST RADA