The selective inhibition of phosphatases by natural toxins: the anhydride domain of tautomycin is not a primary factor in controlling PP1/PP2A selectivity.
Analogues of the potent and moderately selective PP1/PP2A inhibitor tautomycin (TM) were prepared with modifications in the C1'-C7' anhydride moiety. While all retain varying degrees of activity within a 3000-fold range of potencies, they also show remarkable constancy in their IC(50) ratios, suggesting that the anhydride moiety is not critical in controlling the selectivity of inhibition.
Liu
Wen
W
Department of Chemistry, University of California at Irvine, Irvine, CA 92697, USA.
Sheppeck
James E
JE
Colby
David A
DA
Huang
Hsien-Bin
HB
Nairn
Angus C
AC
Chamberlin
A Richard
AR
D000812:Anhydrides / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D008968:Molecular Conformation; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D011714:Pyrans / Q000138:chemical synthesis / Q000737:chemistry*; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014118:Toxins, Biological / Q000737:chemistry*
D000812:Anhydrides; D004791:Enzyme Inhibitors; D011714:Pyrans; D013141:Spiro Compounds; D014118:Toxins, Biological; C053079:tautomycin; D010749:Phosphoprotein Phosphatases