Automated Flow Synthesis of Peptide–PNA Conjugates
Name
acscentsci.1c01019.pdf
Description
Published version
Size
6.02 MB
Format
Adobe PDF
Checksum (MD5)
6c2c3524aa8c2689b4264e93cfd53046
Author(s)
Li, Chengxi
Callahan, Alex J
Phadke, Kruttika S
Bellaire, Bryan
Farquhar, Charlotte E
Zhang, Genwei
Schissel, Carly K
Mijalis, Alexander J
Hartrampf, Nina
Loas, Andrei
Date Issued
February 23, 2022
Journal
ACS Central Science
Publisher
American Chemical Society (ACS)
Citation
Li, Chengxi, Callahan, Alex J, Phadke, Kruttika S, Bellaire, Bryan, Farquhar, Charlotte E et al. 2022. "Automated Flow Synthesis of Peptide–PNA Conjugates." ACS Central Science, 8 (2).
Version
Final published version
Abstract
Antisense peptide nucleic acids (PNAs) have yet to translate to the clinic because of poor cellular uptake, limited solubility, and rapid elimination. Cell-penetrating peptides (CPPs) covalently attached to PNAs may facilitate clinical development by improving uptake into cells. We report an efficient technology that utilizes a fully automated fast-flow instrument to manufacture CPP-conjugated PNAs (PPNAs) in a single shot. The machine is rapid, with each amide bond being formed in 10 s. Anti-IVS2-654 PPNA synthesized with this instrument presented threefold activity compared to transfected PNA in a splice-correction assay. We demonstrated the utility of this approach by chemically synthesizing eight anti-SARS-CoV-2 PPNAs in 1 day. A PPNA targeting the 5' untranslated region of SARS-CoV-2 genomic RNA reduced the viral titer by over 95% in a live virus infection assay (IC50 = 0.8 μM). Our technology can deliver PPNA candidates to further investigate their potential as antiviral agents.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1021/acscentsci.1c01019
