Hi, people interested in high-throughput screening of enzyme inhibitors
might be interested in reading a paper currently in press in Analytical
Biochemistry:
http://www.biokin.com/papers/AB99-0564/
The journal (don't know the volume or issue number yet) should appear in
libraries a few months from now. Here is the abstract:
_________________________________________________________
High-throughput screening of enzyme inhibitors:
Automatic determination of tight-binding inhibition constants
Petr Kuzmic 1,*, Steve Sideris 2, Lynne M. Cregar 2, Kyle
C. Elrod 2, Kenneth D. Rice 3, and James W. Janc 2
1 BioKin, Ltd., P.O. Box 8336, Madison, WI 53708
2 Department of Enzymology and
3 Department of Medicinal Chemistry
Axys Pharmaceuticals, Inc., 180 Kimball Way, South
San Francisco, CA 94080
ABSTRACT
Determination of tight-binding inhibition constants by
nonlinear least-squares regression requires sufficiently
good initial estimates of the best-fit values. Normally an
initial estimate of the inhibition constant must be provided
by the investigator. This paper describes an automatic
procedure for the estimation of tight-binding inhibition
constants directly from dose-response data. Because the
procedure does not require human intervention, it was
incorporated into an algorithm for high-throughput
screening of enzyme inhibitors. A suitable computer
program is available electronically
(http://www.biokin.com). Representative experimental
data are shown for the inhibition of human mast-cell
tryptase.
_____________________________________________________________________
Petr Kuzmic, Ph.D. * BioKin, Ltd. * Consulting & Software Development
http://www.biokin.com * (608) 256-4790 * (608) 256-1269 FAX
