Boc-N-methyl-L-glutamic acid γ-benzyl ester

Polymeric nano aggregates based on poly(L-lysine)-block-PBLG-graft-poly(ethylene glycol) (PLL-b-PBLG-g-PEG) copolymers were prepared by a dialysis method in deionized water. PLL-b-PBLG-g-PEG copolymers with different degrees of PEG substitution were synthesized by combining the ring-opening polymerization of α-amino acid N-carboxyanhydrides and ester exchange reactions. Proton nuclear magnetic resonance spectroscopy and gel permeation chromatography were employed to confirm the polymer structures and molecular weights. Transmission electron microscopy and dynamic light scattering were used to observe the self-assembly behavior. The experimental results revealed that the volume content of deionized water in the mixture significantly affects the morphology and size of the aggregates formed by PLL-b-PBLG-g-PEG copolymers. Spherical, spindle-like, needle-like, and daisy-like aggregates were observed with an increase in the volume content of deionized water in the mixture.

Biodegradable and biocompatible composites are of great interest as biomedical materials for various regeneration processes such as the regeneration of bones, cartilage and soft tissues. Modification of the filler surface can improve its compatibility with the polymer matrix, and, as a result, the characteristics and properties of composite materials. This work is devoted to the synthesis and modification of aminated graphene with oligomers of glutamic acid and their use for the preparation of composite materials based on poly(ε-caprolactone). Ring-opening polymerization of N-carboxyanhydride of glutamic acid γ-benzyl ester was used to graft oligomers of glutamic acid from the surface of aminated graphene. The success of the modification was confirmed by Fourier-transform infrared and X-ray photoelectron spectroscopy as well as thermogravimetric analysis. In addition, the dispersions of neat and modified aminated graphene were analyzed by dynamic and electrophoretic light scattering to monitor changes in the characteristics due to modification. The poly(ε-caprolactone) films filled with neat and modified aminated graphene were manufactured and carefully characterized for their mechanical and biological properties. Grafting of glutamic acid oligomers from the surface of aminated graphene improved the distribution of the filler in the polymer matrix that, in turn, positively affected the mechanical properties of composite materials in comparison to ones containing the unmodified filler. Moreover, the modification improved the biocompatibility of the filler with human MG-63 osteoblast-like cells.

The acidic tumor microenvironment in melanoma drives immune evasion by up-regulating cyclic adenosine monophosphate (cAMP) in tumor-infiltrating monocytes. Here we show that the release of non-toxic concentrations of an adenylate cyclase (AC) inhibitor from poly(sarcosine)-block-poly(L-glutamic acid γ-benzyl ester) (polypept(o)id) copolymer micelles restores antitumor immunity. In combination with selective, non-therapeutic regulatory T cell depletion, AC inhibitor micelles achieve a complete remission of established B16-F10-OVA tumors. Single-cell sequencing of melanoma-infiltrating immune cells shows that AC inhibitor micelles reduce the number of anti-inflammatory myeloid cells and checkpoint receptor expression on T cells. AC inhibitor micelles thus represent an immunotherapeutic measure to counteract melanoma immune escape.