Recombinant production of proteoglycans and their bioactive domains

Abstract

Proteoglycans are ubiquitous dynamic molecules that are made up of a protein core to which specific linear glycosylation structures, known as glycosaminoglycans, have been covalently coupled. They have roles in many biological and pathological processes, which have been shown to be dependent on events involving the protein component and/or the glycosaminoglycan chains. This review focuses on the literature describing the recombinant expression and production of proteoglycans known to be present in the extracellular, cell surface and intracellular environments with an emphasis on how the structure of the molecule relates to its biological function and how this relationship has been explored using recombinant DNA technology for clinical applications.

Glycosaminoglycan and Proteoglycan Biotherapeutics in Articular Cartilage Protection and Repair Strategies: Novel Approaches to Visco‐supplementation in Orthobiologics

“…[47] A number of recombinant PGs have been successfully produced. [46,142] Reproducing GAG fine structures attached to recombinant core proteins to recapitulate native GAG structure is a challenging exercise. Production of recombinant, large PGs such as aggrecan and perlecan have their own technical difficulties associated with their massive molecular dimensions and glycosylation characteristics.…”

Recombinant Domain V of Human Perlecan Is a Bioactive Vascular Proteoglycan

“…[6] Recombinant forms of perlecan domain V have been expressed using human, mouse and drosophila (domain V homologue unc-52) sequences in bacterial and mammalian expression systems. [6] Human domain V sequence encompassing Glu3687 to Ser4391 expressed in HEK-293 cells produced a GAG-free protein core form of domain V, which was named endorepellin (Figure 1). Interestingly, when either mouse domain V sequence, [7][8][9] or human domain V sequence encompassing 37 amino acids into the C-terminal region of domain IV (Leu3626 to Ser4391) named recombinant domain V (rDV) [10] was expressed in HEK-293 cells it resulted in a proteoglycan form of domain V, decorated either with heparan sulfate (HS) or chondroitin sulfate (CS) GAG chains ( Figure 1).…”

In vitro isolation of variants of herpes simplex virus attenuated with altered thymidine kinase and DNA polymerase genes using carrageenans as selection agents

“…Polysaccharide moieties of proteoglycans constitute complex molecules that may be capable of storing functional information for the cell. A number of investigations have shown that carbohydrate chains of proteoglycans are chemically heterogeneous and structurally irregular, and that the informational content of proteoglycans provides a chemical basis for their intricate and highly specific functions in cellular physiology (Gagneux and Varki 1999;Lord and Whitelock 2013;Paulson 1989). Other studies have shown that these same compounds can play important roles in the interactions of microbes and important human diseases (Tiwari et al 2012).…”