Neutral-pH pNZ Removal Enables Fully Aqueous Solid-Phase Synthesis of Linear and ε-Lys-Branched Peptides

Abstract

Aiming to emulate Nature by synthesizing peptides in water, we report pH ∼ 7 Na2S2O4/DIEA-induced pNZ removals as a means of enabling fully aqueous solid-phase peptide synthesis (SPPS). Furthermore, pNZ removal in water was applied to SPPS of ε-Lys-branched peptides and hybrid pNZ/Fmoc SPPS. Finally, combining our methods for SPPS in water with TFA-free resin cleavages opens the door to fully aqueous, PFAS-free approaches to a variety of complex peptides.

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BibTeX RIS

BibTeX

@article{pawlas2026neutralph,
  title = {{Neutral-pH pNZ Removal Enables Fully Aqueous Solid-Phase Synthesis of Linear and ε-Lys-Branched Peptides}},
  author = {Jan Pawlas and Linnea Wahlqvist and Olov Nilsson and Linda M. Haugaard-Kedström},
  journal = {ACS Omega},
  year = {2026},
  month = nov,
  doi = {10.1021/acsomega.6c08146},
  url = {https://pubs.acs.org/acsodf/article/doi/10.1021/acsomega.6c08146/5465396/Neutral-pH-pNZ-Removal-Enables-Fully-Aqueous-Solid},
  note = {CC BY-NC-ND 4.0},
}

RIS

TY  - JOUR
TI  - Neutral-pH pNZ Removal Enables Fully Aqueous Solid-Phase Synthesis of Linear and ε-Lys-Branched Peptides
AU  - Jan Pawlas
AU  - Linnea Wahlqvist
AU  - Olov Nilsson
AU  - Linda M. Haugaard-Kedström
PY  - 2026
DA  - 2026/11/06
JO  - ACS Omega
DO  - 10.1021/acsomega.6c08146
UR  - https://pubs.acs.org/acsodf/article/doi/10.1021/acsomega.6c08146/5465396/Neutral-pH-pNZ-Removal-Enables-Fully-Aqueous-Solid
AB  - Aiming to emulate Nature by synthesizing peptides in water, we report pH ∼ 7 Na2S2O4/DIEA-induced pNZ removals as a means of enabling fully aqueous solid-phase peptide synthesis (SPPS). Furthermore, pNZ removal in water was applied to SPPS of ε-Lys-branched peptides and hybrid pNZ/Fmoc SPPS. Finally, combining our methods for SPPS in water with TFA-free resin cleavages opens the door to fully aqueous, PFAS-free approaches to a variety of complex peptides.
SN  - 2470-1343
ER  -

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