Facile synthesis of AA'B- and ABC-type polypept(o)ide miktoarm star polymers utilizing polysarcosine end group functionalization for core introduction

Miktoarm star polymers display asymmetric architectures with combinations of multiple polymeric arms of different chemical nature emanating from a shared core. Their unique structure–property relationships in comparison to linear counterparts (with same molecular weight) make these architectures interesting for the design of novel polymeric species and the development of nanosized delivery systems. However, the synthesis of such structures is often demanding. Based on polypept(o)ides, we herein report on the synthesis of AA'B- and ABC-type miktoarm star polymers by introducing a multifunctional lysine end group to a polysarcosine (pSar) chain end, comprising orthogonal amine-protective groups. Therefore, each polymeric arm could be synthesized separately by living ring-opening polymerization (ROP) of respective N-carboxyanhydrides (NCAs), offering high reaction control and a resulting structure completely based on amino acids. We demonstrate the utility and versatility of this approach by designing a small, asymmetric and big AA'B miktoarm star polymer comprising two pSar arms with chain lengths of ∼50 or ∼150 in different combinations and a poly(Nε-trifluoroacetate-lysine) (pLys(TFA)) arm, as well as an ABC architecture by introducing a poly(γ-benzyl-glutamate) (pGlu(OBn)). 1H NMR, including 1H DOSY experiments, as well as size-exclusion chromatography (SEC) proof the successful and controlled synthesis of asymmetric miktoarm star polymers with precise control over degree of polymerization of the individual arms with narrow molecular weight distributions.