Toward Quantitative End-Group Fidelity in the Synthesis of High Molecular Weight Polysarcosine DOI Creative Commons

Zlata Nagorna,

Matthias Barz, Joachim F. R. Van Guyse

et al.

ACS Macro Letters, Journal Year: 2025, Volume and Issue: unknown, P. 532 - 537

Published: April 15, 2025

Polymers applied in pharmaceutical applications need to meet stringent quality standards ensure reproducibility of product properties, such as efficacy and safety therapeutics. End-group fidelity is a crucial feature that ensures functional integrity, reproducible synthesis, robust therapeutic performance. The contemporary production poly(ethylene glycol) (PEG) exemplifies this requirement, which has consolidated its position gold standard applications. However, modest severe immune responses toward PEG patients generate the for alternative polymers development pharmaceuticals or cosmetics. Among alternatives, polysarcosine (pSar) displays PEG-like stealth properties vivo while displaying improved immunogenicity toxicity profiles, generating heterotelechelic pSar highest end-group integrity. Here, we compared current synthetic methods controlled synthesis over broad molecular weight range assessed by ion exchange chromatography. Subsequent isolation allowed identification impurities via mass spectrometry, thus yielding mechanistic insights into N-substituted N-carboxyanhydride ring-opening polymerization (ROP). Our results reveal nuanced role organocatalysts ROP, highlighting opportunities better catalysts. Finally, work showcases scalable purification method obtain high with quantitative fidelity.

Language: Английский

Toward Quantitative End-Group Fidelity in the Synthesis of High Molecular Weight Polysarcosine DOI Creative Commons

Zlata Nagorna,

Matthias Barz, Joachim F. R. Van Guyse

et al.

ACS Macro Letters, Journal Year: 2025, Volume and Issue: unknown, P. 532 - 537

Published: April 15, 2025

Polymers applied in pharmaceutical applications need to meet stringent quality standards ensure reproducibility of product properties, such as efficacy and safety therapeutics. End-group fidelity is a crucial feature that ensures functional integrity, reproducible synthesis, robust therapeutic performance. The contemporary production poly(ethylene glycol) (PEG) exemplifies this requirement, which has consolidated its position gold standard applications. However, modest severe immune responses toward PEG patients generate the for alternative polymers development pharmaceuticals or cosmetics. Among alternatives, polysarcosine (pSar) displays PEG-like stealth properties vivo while displaying improved immunogenicity toxicity profiles, generating heterotelechelic pSar highest end-group integrity. Here, we compared current synthetic methods controlled synthesis over broad molecular weight range assessed by ion exchange chromatography. Subsequent isolation allowed identification impurities via mass spectrometry, thus yielding mechanistic insights into N-substituted N-carboxyanhydride ring-opening polymerization (ROP). Our results reveal nuanced role organocatalysts ROP, highlighting opportunities better catalysts. Finally, work showcases scalable purification method obtain high with quantitative fidelity.

Language: Английский

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