Lectins are proteins found in the body that specifically interact with carbohydrate sugars located in, on the surface of and in between cells. This interaction causes the cells to change behavior, including cell movement, multiplication, and other cellular functions. The interactions between lectins and their target carbohydrate sugars occurs via a carbohydrate recognition domain (CRD) within the lectin. Galectins are a subfamily of lectins that have a CRD that bind specifically to β-galactoside sugar molecules. Galectins have a broad range of functions, including mediation of cell survival and adhesion, promotion of cell-cell interactions, growth of blood vessels, immune regulation andinflammation.
There are currently 15 known mammalian galectins, which can be divided into three subclasses, those with one CRD (galectins 1, 2, 5, 7, 10, 13, 14, and 15), those with two CRD (galectins 4, 6, 8, 9 and 12) and those with one CRD and a second domain comprising an amino acid tail (galectin 3) as depicted in Figure 1. At low concentrations, galectins exist as monomers but can exist as dimers and oligomers at higher concentration (Figure 2) and thus form lattic-like networks with β-galactoside containing receptors within a cell and between the cell and its environment (Figure 3). As such, at low concentrations, galectins may have a different biological function, that changes upon up-regulation and over-expression (high concentration, ability to form lattice-like network).
In addition to their concentration dependent functionality, each galectin subtype differs in specificity toward molecules adjacent to the CRD specific β-galactoside sugar molecule, thus further differentiating their functionality. Thus it may be possible to target individual galectins to manipulate the biological outcomes for which they effect.
The role of galectins in pathological disorders is an emerging science. Of the 15 galectins, galectin-3 has been studied most extensively. Galectin-3 is a soluble protein of approximately 30 kDa and is unique as it has both a CRD and a proline rich domain and can form oligomers when binding to multiple β-galactoside containing receptors (in a concentration dependent manner).
Over-expression of galectin-3 has been implicated in a number of human diseases including cancer and chronic organ failure. As such, this makes modulation of the activity of galectin-3 and attractive target for therapy in these diseases. Based on the preceding, La Jolla’s initial programs will focus on modulation of galectin-3 in cancer using GCS-100, a complex polysaccharide which binds to and blocks the effects of galectin-3.
- Publications on galectins can be found here.
- Publications on the role of galectins in cancer can be found here.
- Publications on the role of galectins in chronic organ failure can be found here.