Biocatalyzed Synthesis of Glycostructures with Anti-infective Activity

Area of Science:

• Biochemistry and Medicinal Chemistry
• Carbohydrate Chemistry and Glycobiology
• Sustainable Pharmaceutical Synthesis

Background:

• Carbohydrate-containing molecules are crucial for combating bacterial and viral infections.
• Conventional chemical synthesis of carbohydrate-based drugs faces challenges including multi-step processes, hazardous reagents, and environmental concerns.
• There is a growing need for sustainable and efficient methods in drug discovery and development.

Purpose of the Study:

• To review recent biocatalytic and sustainable approaches for synthesizing carbohydrate-based drugs.
• To highlight the application of enzymes in creating antiviral nucleosides, nucleotides, antibiotics, and glycoconjugates.
• To discuss the potential of these methods in addressing infectious diseases and antibiotic resistance.

Main Methods:

• Utilizing enzymes such as glycosidases, glycosyltransferases (Gtfs), lipases, and nucleoside phosphorylases (NPs) as biocatalysts.
• Employing transglycosylation processes mediated by NPs and N-deoxyribosyltransferases for antiviral nucleoside synthesis.
• Chemoenzymatic synthesis of glycoconjugates (glycovaccines, glycodendrimers) using various enzymes.
• Leveraging Gtfs from natural glycosylated antibiotics for semisynthesis of novel antibiotic derivatives.
• Exploring combinatorial biosynthesis for in vivo synthesis of new drug derivatives.

Main Results:

• Biocatalytic methods enable the efficient synthesis of nucleoside analogues with antiviral activity.
• Chemoenzymatic synthesis yields high-purity glycoconjugates with antibacterial and antiviral properties.
• Enzymatic modification of natural antibiotics leads to novel derivatives combating antibiotic resistance.
• Sustainable approaches provide environmentally friendly toolboxes for drug development.

Conclusions:

• Biocatalysis offers a sustainable and efficient alternative to traditional chemical synthesis for carbohydrate-based drugs.
• Enzymatic strategies are crucial for developing novel therapeutics against viral and bacterial infections.
• This field exemplifies how biocatalysis contributes to sustainable development in the pharmaceutical industry and drug discovery.