Glycopeptides and -Mimetics to Detect, Monitor and Inhibit Bacterial and Viral Infections: Recent Advances and Perspectives

Abstract

The initial contact of pathogens with host cells is usually mediated by their adhesion to glycan structures present on the cell surface in order to enable infection. Furthermore, glycans play important roles in the modulation of the host immune responses to infection. Understanding the carbohydrate-pathogen interactions are of importance for the development of novel and efficient strategies to either prevent, or interfere with pathogenic infection. Synthetic glycopeptides and mimetics thereof are capable of imitating the multivalent display of carbohydrates at the cell surface, which have become an important objective of research over the last decade. Glycopeptide based constructs may function as vaccines or anti-adhesive agents that interfere with the ability of pathogens to adhere to the host cell glycans and thus possess the potential to improve or replace treatments that suffer from resistance. Additionally, synthetic glycopeptides are used as tools for epitope mapping of antibodies directed against structures present on various pathogens and have become important to improve serodiagnostic methods and to develop novel epitope-based vaccines. This review will provide an overview of the most recent advances in the synthesis and application of glycopeptides and glycopeptide mimetics exhibiting a peptide-like backbone in glycobiology.

Stronger Together: Multivalent Phage Capsids Inhibit Virus Entry

“…For this, a variety of platforms have been evaluated as useful scaffolds for conjugation of carbohydrates to create different multivalent systems where the size, shape, and valency (number of carbohydrates) are perfectly controlled [4,5] . Initial compounds were based on the repetition of the sugar motif on a polymeric linear scaffold, such as polyacrylamide, [2] focusing mostly on the number of carbohydrates and less on the control of their disposition.…”

Multivalent Fucosides Targeting β-Propeller Lectins from Lung Pathogens with Promising Anti-Adhesive Properties

“…Among all innovative alternatives to antimicrobials to tackle infections, the carbohydrate-based anti-adhesive approach is still considered underexplored. , Anti-adhesive agents are designed to prohibit the long-lasting attachment of a microbe on the host cell’s surface, therefore preventing infection without generating selective pressure upon the pathogen . Microbes initially attach to the host cells via the action of surface lectins, which are carbohydrate-binding proteins which recognize specific glycan patterns on the cellular surface .…”

Glycans in drug discovery

“…Consequently, the synthetic preparation of homogeneous glycopeptides and glycoproteins has been pursued and allows extension of the overview beyond the “elemental” sugar–protein recognition phenomenon. In fact, synthetic glycopeptides also known as neoglycopeptides, capable of imitating the multivalent display of carbohydrates at the cell surface, have become an important objective as therapeutic compounds, and several reports appeared in the past years about targeting medically relevant lectins 85. Glycopeptide dendrimers,86 glycopeptide nanoparticles87 or glycopolyproline scaffolds88 have been successfully designed to enhance lectin avidity.…”