Abstract：
:Two new monocyclic analogs of the natural AChE inhibitor cyclophostin and two exocyclic enol phosphates were synthesized. The potencies and mechanisms of inhibition of the bicyclic and monocyclic enol phosphonates and the exocyclic enol phosphates toward human AChE are examined. One diastereoisomer of the bicyclic phosphonate exhibits an IC(50) of 3 microM. Potency is only preserved when the cyclic enol phosphonate is intact and conjugated to an ester. Kinetic analysis indicates both a binding and a slow inactivation step for all active compounds. Mass spectrometric analysis indicates that the active site Ser is indeed phosphorylated by the bicyclic phosphonate.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Dutta S,Malla RK,Bandyopadhyay S,Spilling CD,Dupureur CMdoi
10.1016/j.bmc.2010.01.063subject
Has Abstractpub_date
2010-03-15 00:00:00pages
2265-2274issue
6eissn
0968-0896issn
1464-3391pii
S0968-0896(10)00094-5journal_volume
18pub_type
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