Samuel H. Gellman

Samuel Gellman

Vilas Research Professor
University of Wisconsin at Madison
Madison, WI


Foldamer Catalysis

The broad range of activities displayed by the "biofoldamers," proteins and RNA, establishes a set of functional goals to be approached with synthetic foldamers. Enzymes and ribozymes catalyze diverse reactions, often with extraordinary accelerations relative to background rates. The mechanisms by which rates are enhanced vary depending upon the reaction that is catalyzed, and a full accounting for enzymatic rate accelerations remains a subject of debate.

Nevertheless, key principles are evident that suggest paths toward development of synthetic foldamer catalysts. Most enzyme active sites present arrays of reaction-facilitating functional groups that are spatially organized for coordinated action on the substrate/s. Our search for new foldamer catalysts focuses on achieving an optimal arrangement of just two reaction groups, such as optimal bifunctional catalysis.

Initial studies employed a simple crossed aldol reaction, in which formaldehyde is the obligate electrophile, to assay alternative arrangements of pairs of pyrrolidine units presented by distinct β– and α/&beta-peptide helices. The most effective foldamer contained an αββ backbone repeat with i,i+3 spacing between pyrrolidine-based β residues.

Mechanistic analysis supported a catalytic cycle that features covalent activation of both substrates by a single foldamer molecule. Recent work has focused on bifunctional foldamers that catalyze aldol reactions resulting in formation of macrocycles.


Samuel H. Gellman


University of Wisconsin at Madison, Department of Chemistry

Lecture Images

Samuel Gellman presenting at APS2019 Samuel Gellman presenting at APS2019 Samuel Gellman presenting at APS2019