Samuel H. Gellman

Professor Samuel H. Gellman pioneered the field of foldamers, demonstrating that unnatural oligomers can adopt stable, predictable secondary structures with protein-like functions. His work on β-peptides and α/β-peptides established design principles for creating molecules that resist proteolysis while retaining biological activity.

Gellman is a faculty member in the Department of Chemistry at the University of Wisconsin-Madison. His research integrates asymmetric organic synthesis, biophysical characterization and cell-based assays to create and evaluate new molecular architectures.

In 1996, Gellman reported that oligomers of β-amino acids form robust helical structures in solution. Unlike natural α-helices, these β-peptide helices display novel hydrogen-bonding patterns and can be tuned by varying the position and stereochemistry of side chain substitution. His group demonstrated that β-peptides containing as few as six residues form stable 3₁₄-helices with remarkably slow amide proton exchange.

Building on these discoveries, Gellman developed α/β-peptides that combine α- and β-amino acid residues in regular patterns. Crystal structures revealed that these chimeric foldamers bind target proteins at recognition surfaces normally engaged by natural α-helices. Critically, the α/β-peptides resist degradation by proteases, addressing a major limitation of peptide-based therapeutics.

His laboratory designed foldamers that inhibit HIV fusion by targeting the gp41 protein and disrupt antiapoptotic Bcl-x_L interactions relevant to cancer. The group also developed antimicrobial nylon-3 polymers and membrane protein-stabilizing amphiphiles. Gellman co-founded Longevity Biotech to pursue biomedical applications of α/β-peptide technology.