Heparin sulfate interactions with proteins

Both heparin and heparan sulfate interact with CS protein and help in the binding of the parasite to liver cells. Surface plasmon resonance (SPR) experiments indicate that heparin has fast on-rate k and slow off-rate (kd) kinetics for CS protein with a of 41 nM. Isothermal titration calorimetry shows that the minimum sequence within the heparin polymer capable of a strong interaction with the CS protein is a decasaccharide. High concentrations of exogenous heparin or heparan sulfate can inhibit the binding of CS protein to HepG2 cell, a human hepatoma cell line. However, at low concentrations, heparin or heparan sulfate can also act as a... 

Heparin sulfate proteoglycans (HSPGs) are heavily glycosylated proteins that are part of the extracellular matrix. Interaction with HSPGs help to stabilize and localize extracellular Wnts. 

It is likely that the predominantly positively charged amino acids of TAT and other CPPs will interact with anionic components on the surface of the cell membrane (85). This idea is supported by the observation that cell association with CPP liposomes in glycosaminoglycan-deficient Chinese hamster ovary (CHO) cells is greatly reduced and is competitively inhibited by the presence of heparin (88,93). Furthermore, the removal of the heparan sulfate chains by the action of glycosaminoglycan lyase also suppressed the transduction of the TAT protein (94). 

Heparinoid polysaccharides such as heparan sulfate and heparin are able to interact with numerous proteins and influence vital biological processes. Heparinoid mimetics were prepared to reduce the structural complexity of heparinoids and to obtain selectivities. This article summarizes the development of heparinoid mimetics of different classes including representative syntheses and biological activities. Largely simplified compounds with regard to structure and synthetic access are described which maintain or exceed the activity of heparinoid polysaccharides. One of the recipes to increase binding or modify pharmacokinetic parameters was the introduction of hydrophobic groups. 

Table 1 Binding interactions of heparin/hepaian sulfate with proteins (incomplete listing) ...

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