D.K.Yuryev's homepage
click to download file crsaf_02.zip with
completely operational program (about 80 K)
popular illustrated theory on this program (MS Word
format, about 40K) is now also available
Dmitriy K. Yuryev
e-mail: yur77@glas.apc.org
Identification of new receptor subtypes that may mediate some function of human organism is an important standard problem in pharmacology. Progress in this field is dealt with receptor cloning techique which, roughly speaking, allows to obtain every receptor in purified form. This present work proposes a so called cross-titration experiment which opens an alternative way (cheap yet less powerful) making possible to identify 4-5 subtypes coexisting in mixture.
A new type of ligand-binding experiment called cross-titration experiment is being proposed for characterization of tissues containing multiple receptor subtypes. It is an extension of traditional inhibition experiment employing two different inhibitors at once: binding of a constant amount of labeled ligand is measured in approximately 10x10 array of wells where concentration of one inhibitor is varying in rows and concentration of another one - in columns.
The program CROSAFIN recovers from such data a two-dimensional distribution of receptor subtypes on the coordinate plane with affinity constant to one inhibitor on X-axis and to the second inhibitor - on Y-axis. Routinely, this method ensures a problem-free dealing with tissues containing 4-5 receptor subtypes, though, of course, still much depends upon availability of inhibitors with appropriate affinity profiles.
Documentation also contains (MS Word 6.0 for Windows format) two critical
articles on traditional tecniques of affinity analysis. Click to read the
abstracts:
Absurd Trivial Errors in Scatchard Plot Analysis
Refining Cheng-Prusoff Equation
Here are several pictures produced by the program: some simulated dataset
derived from 4-site model and the calculated affinity map in two graphical
presentations.
