Development of Improved Synthetic Routes to Pixatimod (PG545), a Sulfated Oligosaccharide-Steroid Conjugate.
Bioconjug Chem
; 32(11): 2420-2431, 2021 11 17.
Article
in English
| MEDLINE | ID: covidwho-1526037
ABSTRACT
The heparan sulfate (HS) mimetic pixatimod (PG545) is a highly potent inhibitor of angiogenesis, tumor growth, and metastasis currently in clinical trials for cancer. PG545 has also demonstrated potent antiviral activity against numerous HS-dependent viruses, including SARS-CoV-2, and shows promise as an antiviral drug for the treatment of COVID-19. Structurally, PG545 consists of a fully sulfated tetrasaccharide conjugated to the steroid 5α-cholestan-3ß-ol. The reported synthesis of PG545 suffers from a low yield and poor selectivity in the critical glycosylation step. Given its clinical importance, new efficient routes for the synthesis of PG545 and analogues were developed. Particular attention was given to improving the key glycosylation step by using more stable protecting groups and optimized glycosyl donors.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
COVID-19
Type of study:
Experimental Studies
/
Prognostic study
/
Randomized controlled trials
Limits:
Humans
Language:
English
Journal:
Bioconjug Chem
Journal subject:
Biochemistry
Year:
2021
Document Type:
Article
Affiliation country:
Acs.bioconjchem.1c00453
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