On the origin of the low immunogenicity and biosafety of a neutral α-helical polypeptide as an alternative to polyethylene glycol

Impact of the Hydrophilicity of Poly(sarcosine) on Poly(ethylene glycol) (PEG) for the Suppression of Anti-PEG Antibody Binding

“…Then, the solutions were removed, and the plate wells were washed with a wash solution (50 mM tris-buffered saline (TBS), pH = 8.0) 3 times. Since TWEEN as a surfactant in the buffer is commonly used in ELISA and contains PEG, , therefore, we should use [3-(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, (CHAPS) instead.…”

Research progress on the PEGylation of therapeutic proteins and peptides (TPPs)

“…It should be noted that PEGylated molecules with distinct chain structures of linear and branched chains have various biological characteristics that can affect numerous pharmacokinetic parameters of TPPs (Vugmeyster et al, 2012;Zhang et al, 2012). Branched PEG modifiers exhibit reduced accessibility to hidden sites and enhanced stability against proteolysis compared to linear PEG modifiers (Wan et al, 2017;Sun et al, 2023).…”

Conformation-Switchable Polypeptides as Molecular Gates for Controllable Drug Release

“…Synthetic polypeptides have displayed great potentials in the biomedical field and are regarded as promising candidates for the design of drug carriers due to their desired biocompatibility and biodegradability. − As protein mimics, polypeptides can adopt ordered secondary structures (e.g., α-helix and β-sheet) through hydrogen bonding interactions between backbone peptide bonds, − which endow them with conformation-specific assembly behaviors and biomedical functions. − For instance, cationic polypeptides with α-helical structures exhibit much higher membrane-penetrating activity than their random-coiled analogues, which are internalized through the “pore-formation” mechanism. − Through proper side-chain design, α-helical, cationic polypeptides have been widely studied to promote the intracellular delivery of molecular cargos or to facilitate the design of antimicrobial or antitumor polymers. − Additionally, amphiphilic polypeptides with α-helical hydrophobic segments tend to self-assemble into vesicles due to the parallel arrangement of rigid helices, while their β-sheet and random-coiled analogues are more likely to form micelles. ,, Due to the distinct differences of materials properties between helical and random-coiled conformation, conformation-switchable polypeptides are designed and synthesized to manipulate their biomedical functions in situ . The transition of secondary structures is achieved through the fine-tuning of side-chain interactions including electrostatic interactions, − polarity, − hydrogen bonds, coordination interaction, and base-pairing interactions, which activates or deactivates the helix-associated functions under desired conditions.…”