Heparan sulfate: biological significance, tools for biochemical analysis and structural characterization

Abstract

Heparan sulfate (HS) and heparin (HP) are functionally important glycosaminoglycans, which interact with a plethora of proteins and participate in several cellular events. They form specific proteoglycans, which are ubiquitously distributed at both extracellular and cellular levels. HS and HP chains vary in the sulfation pattern and the degree of C-5 epimerization of d-glucuronic acid to l-iduronic acid. These modifications are not uniformly distributed within the chain, providing functional oligomeric domains interacting specifically with various effective proteins. The utilization of specific lyases and chemical depolymerization are the commonest procedures used for structural analysis. Di- and oligosaccharide composition of HS can be accurately and sensitively determined by HPLC, CE and MS. Ultraviolet detection is satisfactory enough for unsaturated saccharides and pre-column derivatization with fluorophores and detection with laser-induced fluorescence results in even higher sensitivity. Solid-phase assays can also be used for monitoring interactions with other molecules. In this article the biological significance of HS and HP in health and disease as well as the portfolio of analytical methods that may help to a deeper understanding of their roles in various pathological processes is presented. Such methodologies are of crucial importance for disease diagnosis and the design of novel synthetic sugar-based drugs.

miRNA-218 contributes to the regulation of D-glucuronyl C5-epimerase expression in normal and tumor breast tissues

“…D-glucuronyl C5-epimerase (GLCE, NM_015554) is one of the key enzymes in biosynthesis of heparan sulfate proteoglycans (HSPGs), which are involved in cell-cell and cell-matrix interactions, intercellular signaling and appropriate cell microenvironment 1 - 4 . Recently, it was shown that GLCE possesses a tumor-suppressor activity in breast and small-cell lung cancer 4 , 5 and GLCE expression is significantly downregulated in primary breast tumors and in breast and lung cancer cell lines compared with controls 6 , 7 .…”

“…Recently, it was shown that GLCE possesses a tumor-suppressor activity in breast and small-cell lung cancer 4 , 5 and GLCE expression is significantly downregulated in primary breast tumors and in breast and lung cancer cell lines compared with controls 6 , 7 . However, the molecular mechanisms of GLCE inactivation in cancer cells remain unclear.…”

Replication-competent gamma-retrovirus Mo-MuLV expressing green fluorescent protein as efficient tool for screening of inhibitors of retroviruses that use heparan sulfate as primary cell receptor

“…The main difference between heparin from heparan sulfate is its lower degree of sulfonation. The presence of sul fate and carboxyl groups defines the substantial nega tive charge of these biopolymers under neutral condi tions [13,14] It is known that sulfated polysaccharides exhibit high antiviral activity, which prevents them from pene trating cell DNA and RNA containing viruses (her pes simplex virus, human cytomegalovirus, Sindbis virus, and HIV) [15,16]. Generally, polysaccharides with high molecular weights and degrees of sulfona tion have higher antiviral activity [17].…”

Poly(ADP-Ribose)—A Unique Natural Polymer Structural Features, Biological Role and Approaches to the Chemical Synthesis

“…The main difference between heparin and heparan sulfate is the lower degree of sulfonation of the later. [43] Teihoic acids isolated from cell wall of gram-positive bacteria consist of repeating polyol or glycosylpolyol residues joined together with phosphodiester linkages. [44] …”