Mixture-Based Combinatorial Libraries: From Peptides and Peptidomimetics to Small Molecule Acyclic and Heterocyclic Compounds

Abstract

Publisher Summary This chapter focuses on the mixture-based combinatorial libraries. The two major techniques are generally employed in solid-phase chemistry to generate mixture-based synthetic combinatorial libraries (SCL) of millions of compounds. The techniques include “divide-couple-recombine” (DCR) method and the “reagent mixture method.” Multiple functionalities at diverse positions within the library are incorporated either by mixing multiple resins or by using mixtures of incoming reagents. In contrast to the “reagent-mixture” method, the DCR method is more labor and cost intensive, because the amount of resin and work increases proportionally with the number of building blocks incorporated at a particular position. The generation of peptidomimetic libraries by chemical modification of an existing dipeptide library is shown diagrammatically. The two requirements that have to be fulfilled for the chemical modification of an existing library are: (1) one must begin with a well-defined library, and (ii) one must use a chemical reagent that can effectively alter chemical moieties, while leaving either all of the compound mixture on the resin or alternatively removing all of the mixture from the resin.