Rational Design and Engineering of 3-O-Sulfotransferase 1 Based on Enzyme Affinity for Improved Enzymatic Heparin Preparation

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 23, 2025

Heparin, a naturally occurring glycosaminoglycan, is renowned for its potent anticoagulant properties, which are critical various medical applications. A significant determinant of activity the degree 3-O-sulfation. Gaining insight into substrate binding characteristics 3-O-sulfotransferase-1 (3-OST-1) could enhance our understanding sulfotransferase family and facilitate enzymatic preparation heparin. This study aimed to identify mutants 3-OST-1 with improved catalytic activities through rational design. The enzyme W72R H144R were recorded at 26.40 17.21 U/L, respectively, representing increases 1.7 1.1 times compared wild-type (WT) 3-OST-1. Notably, double mutant W72R/H144R reached 34.41 2.2 greater than that WT. heparin modified by exhibited superior properties those WT, demonstrating highest potency. Furthermore, kinetic assays molecular dynamics simulations illustrated enhanced resulted from an increased affinity substrate.

Language: Английский

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Novel Papain-Like Protease Inhibitors for Treating Viral Infections, in Particular Coronavirus Infections

ACS Medicinal Chemistry Letters, Journal Year: 2024, Volume and Issue: 15(11), P. 1802 - 1803

Published: Oct. 14, 2024

Provided herein are novel papain-like protease (PLpro) inhibitors, pharmaceutical compositions, use of such compounds in treating viral infections, particular coronavirus and processes for preparing compounds.

Language: Английский

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Pyrrolidines as Main Protease Inhibitors for Treating Viral Infections, in Particular, Coronavirus Infections

ACS Medicinal Chemistry Letters, Journal Year: 2024, Volume and Issue: 15(12), P. 2097 - 2098

Published: Nov. 15, 2024

Provided herein are novel pyrrolidines as main protease inhibitors, pharmaceutical compositions, use of such compounds in treating viral infections, particular, coronavirus and processes for preparing compounds.

Language: Английский

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