Stable helical beta 3-peptides in water via covalent bridging of side chains

An on-bead cyclization protocol of beta 3-peptides was developed, providing easy access to cyclic beta 3-peptides. With this methodology, a small library of helical cyclic beta 3-peptides was synthesized and investigated with CD spectroscopy. Covalent bridging of two side chains in beta 3-peptides significantly stabilized their helical conformation in aqueous solutions and turned out to be superior to the previously described electrostatic interactions.