Synthesis of Amphiphilic Block Copolypept(o)ides by Bifunctional Initiators: Making PeptoMicelles Redox Sensitive

Abstract

In this work, the synthesis of polypeptoid-block-polypeptide copolymers (block copolypept(o)ides) based on bifunctional initiators is described, which introduces a distinct chemical entity at the connection between both blocks. With a view towards redox-sensitive block copolypept(o)ides, a cystamine-based initiator was used to synthesize polysarcosine macroinitiators with degrees of polymerization (Xn) between 100 and 200 displaying monomodal molecular weight distributions and dispersities (Đ) around 1.1 as determined by size exclusion chromatography. Block copolypept(o)ides with a poly(γ-t-butyloxycarbonyl-L-glutamate) (PGlu(O(t) Bu)) block (Xn = 25 or 50) were synthesized by controlled N-carboxyanhydride polymerization. Resulting block copolymers possess monomodal molecular weight distributions, dispersities around 1.2 and were applied to degradation studies. While block copolypept(o)ides are stable at 10 × 10(-6) M, they degrade over time at GSH concentrations of 10 × 10(-3) and 100 × 10(-3) M. Furthermore, these disulfide-containing block copolymers form PeptoMicelles, which degrade at intracellular GSH concentrations while remaining stable at extracellular GSH levels.

Synthesis and Characterization of Stimuli‐Responsive Star‐Like Polypept(o)ides: Introducing Biodegradable PeptoStars

“…The quasi‐living polymerization provides precise control of molecular weights, high end‐group integrity, and low polymer dispersity. Furthermore, our group has recently introduced stimuli‐responsive polypept(o)ides, which react to changes in reduction potential by disulfide cleavage . The reductive cleavage of the disulfide can be used to convert an amphiphilic block copolymer into its individual blocks, which causes destabilization of the micelle and hence facilitates cargo release.…”

Secondary‐Structure‐Driven Self‐Assembly of Reactive Polypept(o)ides: Controlling Size, Shape, and Function of Core Cross‐Linked Nanostructures

“…[29] This chemoselective reactivity enables core cross-linking through the formation of asymmetric disulfides (Figure 1CII), which seems to be asuitable approach to preserve the morphologies of the formed nanoparticles.P Sar-b-PCys-(SO 2 Et) block copolymers can be obtained by NCAp olymerization with abifunctional initiator as reported previously (see the Supporting Information, Scheme S1). [30] Block copolymers with differing block length ratios and total block lengths were prepared with dispersity indices () between 1.2 and 1.4 (Table S1 and Figure S1). Thes elfassembly of PSar-b-PCys(SO 2 Et) block copolymers was investigated methodically by varying two major factors contributing to the overall morphology,n amely the composition of the amphiphile as well as favoring/suppressing the formation of the secondary structure in the absence/presence of the chaotropic agent thiourea.…”

Polypeptoid polymers: Synthesis, characterization, and properties

“…This area represents a fertile ground for research, as it will provide fundamental understanding of the interactions between polypeptoids and immune systems, which is critical for the further development of polypeptoid biomaterials for in vivo applications. poly(E-N-benzyloxycarbonyl-L-lysine), [99] poly(g-benzyl-L-glutamate), [99] poly(g-tert-butyl-L-glutamate), [100] and poly(S-ethylsulfonyl-L-cystine)], [101] PNMG-b-poly(E-caprolactone), [102] PNMG-b-poly[2-(3-butenyl)-2-oxazoline], [57] PNMG-b-(Leu-Aib) n [(Leu-Aib) n : helical peptides], [103][104][105][106][107][108][109][110] PNMG-b-poly(L-lactide) (AB, A 2 B, A 3 B types), [111] dextran-b-PNMG, [112] PEG-b-PNMG, [42] and C n512-18 -PNMG lipopolymers. [113][114][115] Their solution aggregation behavior has been reviewed by Luxenhofer et al [30] and will not be repeated here.…”