The use of functionalized NCAs allows direct incorporation of biologically relevant functional groups in precise locations in chains, but may require multiple synthetic steps and tedious purification.

Our methodology utilizes methionine NCA, derived from the natural amino acid and readily prepared and polymerized without need of protecting groups. High yield, efficient modification of thioether groups after polymer formation provides a scalable route to highly functional, and biologically relevant polypeptides.

Our lab has discovered that functional polypeptides based on poly(homocysteine) backbones can undergo reversible switching between alpha-helical and disordered conformations via mild, and reversible chemical modifications under biologically relevant conditions.

Using methionine alkylation and demethylation methodology, we prepared a series of oligoethylene glycol functionalized poly(homocysteine) derivatives, all from the same parent poly(methionine) sample. These polymers undergo reversible temperature dependent solubility transitions (lower critical solution temperature behavior) in aqueous media. These and related polypeptides are being developed for use in stimuli responsive block copolypeptide assemblies.