Abstract
Functionalized polypeptides have attracted tremendous interest in recent years and found many important medical applications due to their tunable physico-chemical characteristics including hydrophilicity and stimuli-responsive behavior. Many studies have focused on the synthesis of new side-chain modified (co)polypeptides via post-polymerization click reactions, taking advantage of the side clickable groups. These reactions are highly efficient, selective, mild and tolerant to most functional groups, for that reason they have been powerful tools for modification of biopolymers.
Polypeptides bearing alkyne groups are important precursors to create new polypeptide materials, since the alkyne groups can undergo not only azide-alkyne cycloaddition with a variety of fazide-bearing molecules but also thiol-yne reactions with various thiols. Consequently, the synthesis of well-defined polypeptides with alkyne side-groups remains a challenge in contrast to polypeptides containing protected functional groups, such as poly(γ-benzyl-L-glutamate) and poly(ε-Cbz-L-lysine), which can be only used after deprotection.
Along these lines, a novel metal-free strategy, using hydrogen-bonding catalytic ring opening polymerization of alkyne-functionalized N-carboxy anhydrites of α-amino acids, was developed for the synthesis of well-defined polypeptides bearing pendant alkyne groups. This method provides an efficient way to synthesize novel alkyne-functionalized homopolypeptides (A) and copolypeptides, such as AB diblock (B: non-functionalized), ABA triblock and star-AB diblock, as well as linear and star random copolypeptides, which are precursors of a plethora of complex macromolecular architectures by click chemistry.