American Chemical Society
mz9b00538_si_001.pdf (1.69 MB)

Pyridyl Disulfide Reaction Chemistry: An Efficient Strategy toward Redox-Responsive Cyclic Peptide–Polymer Conjugates

Download (1.69 MB)
journal contribution
posted on 2019-09-27, 18:44 authored by Qiao Song, Jie Yang, Stephen C. L. Hall, Pratik Gurnani, Sébastien Perrier
Cyclic peptide–polymer conjugates are capable of self-assembling into supramolecular polymeric nanotubes driven by the strong multiple hydrogen bonding interactions between the cyclic peptides. In this study, we have engineered responsive nanotubes by introducing a cleavable bond that responds to a reductant utilizing pyridyl disulfide reaction chemistry. Reactions between a cysteine containing cyclic peptide (CP-SH) and pyridyl disulfide containing polymers were initially studied, leading to the quantitative formation of cyclic peptide–polymer conjugates. An asymmetric cyclic peptide–polymer conjugate (PEG-CP-S-S-pPEGA) was then synthesized via orthogonal pyridyl disulfide reaction chemistry and NHS coupling chemistry. The disulfide linker formed by the pyridyl disulfide reaction chemistry was then selectively reduced to thiols in the presence of a reductant, enabling the transition of the conjugates from nonassembling unimers to self-assembled supramolecular polymeric nanotubes. It is anticipated that the pyridyl disulfide reaction chemistry will not only enrich the methodology toward the synthesis of cyclic peptide–polymer conjugates, but also lead to the construction of a new family of redox-responsive cyclic peptide–polymer conjugates and supramolecular polymeric nanotubes with tailored structures and functionalities.