In Vacuo Glycation of Poly(l-Lysine): A Simple Method to Install Pendent Sugars

Abstract

Glycopolymers are valuable for biomedical applications due to their ability to mimic natural glycoconjugates, yet current synthetic methods often require complex chemistries or do not produce native linkages. Here, we report a simple in vacuo glycation method to functionalize poly(l-lysine) (PLL) with pendent sugars, inspired by natural nonenzymatic glycation. PLL was incubated with various reducing sugars in vacuo at elevated temperatures, enabling efficient conjugation via native-like ketoamine linkages without additional chemical modifications or activating agents. The best evaluated conditions for d-glucose involved 4 sugar equivalents, pH 8, and 65 °C, yielding >95% functionalization with minimal advanced glycation end-product (AGE) formation or cross-linking. Aldohexoses such as d-mannose and d-galactose were also successfully conjugated under slightly modified conditions (70 and 60 °C, respectively), while ketoses, pentoses, and trioses led to insoluble, cross-linked products due to increased AGE formation. Reducing disaccharides exhibited limited conversion, likely due to steric hindrance. Structural characterization confirmed efficient sugar installation and preservation of polymer solubility. This in vacuo glycation approach offers a straightforward, biomimetic route to glycopolymer synthesis from amine-bearing polymers, expanding the toolkit for designing bioinspired materials for biomedical and material science applications.