- Pulcu, G. S.; Galenkamp, N. S.; Qing, Y.; Gasparini, G.; Mikhailova, E.; Matile, S.; Bayley, H. “Single-Molecule Kinetics of Growth and Degradation of Cell-Penetrating Poly(disulfide)s” J. Am. Chem. Soc. 2019, 141, 12444-12447
The delivery of therapeutic agents into target cells is a challenging task. Cell penetration and intracellular targeting were recently ad-dressed with biodegradable poly(disulfide)s (CPDs). Cellular localization is determined by the length of these polymers, emphasizing the significance of initial chain length and the kinetics of intracellular depolymerization for targeted delivery. In the present study, the kinetics of CPD polymer growth and degradation were monitored in a single-molecule nanoreactor. The chain lengths achievable un-der synthetic conditions with high concentrations of dithiolanes, were then predicted by using the rate constants. For example, CPDs comprising 40 units are generated in 1 s at pH 7.4 and 0.3 s at pH 8.4 at dithiolane concentrations of 200 mM. The rate constants for degradation suggest that the main depolymerization pathway in the cell is by monomer removal by self-cyclization, rather than by intra-chain cleavage by endogenous thiols.
DOI: 10.1021/jacs.9b00387
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