SEQUENCE-SPECIFIC POLYPEPTOIDS - A DIVERSE FAMILY OF HETEROPOLYMERS WITH STABLE SECONDARY STRUCTURE

We have synthesized and characterized a family of structured oligo-N-s ubstituted-glycines (peptoids) up to 36 residues in length by using an efficient solid-phase protocol to incorporate chemically diverse side chains in a sequence-specific fashion. We investigated polypeptoids c ontaining side chains with a chiral center adjacent to the main chain nitrogen. Some of these sequences have stable secondary structure, des pite the achirality of the polymer backbone and its lack of hydrogen b ond donors. In both aqueous and organic solvents, peptoid oligomers as short as five residues give rise to CD spectra that strongly resemble those of peptide alpha-helices. Differential scanning calorimetry and CD measurements show that polypeptoid secondary structure is highly s table and that unfolding is reversible and cooperative. Thermodynamic parameters obtained for unfolding are similar to those obtained for th e alpha-helix to coil transitions of peptides. This class of biomimeti c polymers may enable the design of self-assembling macromolecules wit h novel structures and functions.