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LIGAND SYNTHESIS FOR TARGETED DEGRADATION OFAbstracts ICPS 2023
LIGAND SYNTHESIS FOR TARGETED DEGRADATION OF
SARS CoV-2 NSP14
Maria А. Zakharova, Mikhail V. Chudinov
MIREA - Russian Technological University, 86 Vernadsky avenue, Moscow, Russia
The technology of targeted protein degradation (Protac©) is based on the production
of chimeric molecules consisting of 2 ligands to various biological targets: to the
element of the proteasome complex ligase E3 and to the target protein. The ligands are
interconnected by a spacer. As a result of the action of such a chimeric molecule, the
target protein is labeled by the E3 ligase as a target of the proteasome complex of the
cell and is further destroyed by the proteasome. This new technology has already proven
itself in the creation of antitumor drugs, but its use in the fight against viruses is just
beginning [1]. Based on the recently developed inhibitors of the nonspecific protein
nsp-14 of the SARS-Cov2 virus [2], we synthesized chimeric compounds
Cov3
and
Cov4
, potentially suitable for use in Protac technology to combat SARS-Cov2
(Schema1)
.
1. Desantis J., Goracci L. Proteolysis targeting chimeras in antiviral research. Future
Med Chem. 2022;14(7):459-62. doi: 10.4155/fmc-2022-0005.
2. Ahmed-Belkacem R., Hausdorff M., Delpal A., Sutto-Ortiz P., Colmant A.M.G.,
Touret F., et al. Potent Inhibition of SARS-CoV-2 nsp14 N7-Methyltransferase by
Sulfonamide-Based Bisubstrate Analogues. J Med Chem. 2022;65(8):6231-49. doi:
10.1021/acs.jmedchem.2c00120.
Poster presentation
63
GROWTH AND BIOCHEMICAL CHARACTERISTICS OF
WINTER WHEAT SEEDLINGS AFTER SEED TREATMENT
WITH CONJUGATE CHITOSAN-CAFFEIC ACID
J.N. Kalatskaja1, N.A. Laman1, K.M. Herasimovich1, K.I. Rybinskaya1,
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