Biocombinatorial Selection of Carbohydrate Binding Agents of Therapeutic Significance

Abstract

Components of the cell-surface and extracellular matrix (including cell walls of some microorganisms) present ideal but often challenging targets for disease detection and targeting. In the past few years, selection of peptide and oligonucleotide biomimics against secreted and extracellular targets has resulted in the isolation of small high affinity binding agents against target molecules. However, little attention has been paid to the interaction of these biomimics with glycans (specifically, cell surface glycans) despite their ubiquitous and abundant presence on every cell (glycocalyx). Although glycans are now accepted as critically important class of molecules as biomarkers, imaging, therapeutic and drug targets, little advance has been made in exploiting these molecules for clinical applications. The diversity and complexity of glycan structures along with time-consuming analytical and synthetic methods are among the most significant challenges faced by glycoscientists. Innovative technologies are urgently needed to overcome these challenges and to develop glycan-based clinical applications. This review article will provide an overview of existing biocombinatorial methods that focus on the selection and use of glycan-binding random oligonucleotide ligands (aptamers) as conceptually novel therapeutics for a variety of biomedical applications including anti-microbial and anti-cancer agents. Given the range and importance of protein-carbohydrate interactions in biological processes, rapid discovery of agents that mediate these interactions may provide fruitful venues towards novel therapeutics.

Cancer glycan biomarkers and their detection – past, present and future

“…86 Aptamers, short nucleotides that bind specic proteins and sugars as well as linear and cyclic peptides, have also been shown to bind carbohydrates. 87,88 Natural antimicrobial peptides, such as defensins, have evolved to bind carbohydrate structures with high affinity and specicity. 89,90 Fully synthetic lectins have also been described.…”

Glycobiomimics and glycobiosensors

“…In vitro selection of specific proteins/peptides occurs by sequential enrichment of bound phage during cycles of biopanning and propagation. There are an increasing number of reports describing the use of phage display for the discovery of biomimetic peptides against carbohydrate and lectin targets [15].…”

Synthetic Glycosylphosphatidylinositol as Tools for Glycoparasitology Research

“…Because parasite cell-surface GPI structures are species specific, they present ideal targets for infection diagnosis and antidisease targeting (Oyelaran et al, 2009b;Svarovsky and Joshi, 2008;Uttamchandani et al, 2008). GPI microarrays are an excellent tool for the rapid evaluation of parasitic disease, monoclonal antibody mapping, as well as the detection of undesired autoantibody reactivity specific for GPIs in autoimmune disorders.…”