Daniel Invents Tools to Enable Switching Functional Groups on Peptides

Dr. Daniel Honeycutt recently completed his Ph.D. in chemistry at the University of Rhode Island, where he trained in Professor Fang Wang’s laboratory. Originally educated as a polymer chemist, Dan pivoted into peptide science in 2020, drawn by the intellectual challenge of working with biomacromolecules whose functional groups and reactive sites present a vastly more complex landscape than traditional small molecules.

During his doctoral work, Dan pioneered new methods to manipulate cysteine residues—long considered one of peptide chemistry’s most versatile but also most limiting side chains. His research produced a remarkably rapid and mild bioconjugation reaction using pyridinium salts, enabling thiol labeling under physiological conditions in mere seconds. He also advanced a suite of reactions for transforming cysteine residues into β-haloalanines within unprotected peptides. These electrophilic handles open up a rich palette of downstream reactivity: direct nucleophilic substitution, transition-metal–mediated cross-coupling, and the construction of halopeptides with novel structures and properties.

As first author on a recent Journal of the American Chemical Society communication, Dan and colleagues introduced the concept of cysteine umpolung, reversing the innate nucleophilicity of the cysteine thiol into an electrophilic iodide. This “polarity inversion” unlocks late-stage peptide modifications that were previously inaccessible, providing a new chemical grammar for building molecular diversity.

Dan’s achievements reflect a larger vision, developing simple yet elegant solutions to complex synthetic problems in peptide science. He anticipates that halopeptide chemistry will find broad application in both discovery science and therapeutic development, expanding the toolkit for engineering biomolecules with precision. Having recently defended his dissertation, Dan looks forward to continuing a research career at the interface of organic synthesis, chemical biology, and translational medicine.

Daniel Honeycutt received his Chemistry Ph.D.in Fang Wang's Group at the University of Rhode Island. He is developing simple yet elegant solutions to complex synthetic problems in peptide science.