Encoding strategies in combinatorial chemistry.

Abstract

To Pasteur’s famous dictum, “Chance favors the prepared mind,” could arguably be added the corollary, “As the number of chances increases, so increases the effect of favor.” It is nearly a truism that a great many important discoveries in chemistry originated not from careful design, but from astute observations of unintended experiments. Suppose, then, that creativity were applied to the task of enormously increasing both the number of “chance” experiments possible and one’s confidence that a “success” would be observable? In essence, that is the philosophy behind the new field called combinatorial chemistry: Design a synthesis experiment that both leads to a large collection of new chemical substances (“molecular diversity”) and affords that collection in a format facilitating the selection of individual members possessing a given property of interest. This paper is organized on our German–American Frontiers of Science session on “Combinatorial Chemistry,” which was held on June 19, 1996, in Munich. The presenters were Michael Famulok of the Ludwig-Maximilians-Universitat, Jon Ellman of the University of California at Berkeley, and the author. J. Ellman has previously published a summary paper in the PNAS on “Combinatorial thinking in chemistry and biology” (1), and so I will not repeat that topic. Instead, I found it of interest that each presenter’s combinatorial chemistry experiments embodied fundamentally different types of encoding strategies . Thus, this paper will summarize the proceedings as a vehicle highlighting the concept of encoding and surveying the merits of different encoding methods. A combinatorial chemistry or biology approach to discovery begins with a large collection …