Functions and Inhibition of Galectin-7, an Emerging Target in Cellular Pathophysiology

Abstract

Galectin-7 is a soluble unglycosylated lectin that is able to bind specifically to β-galactosides. It has been described to be involved in apoptosis, proliferation and differentiation, but also in cell adhesion and migration. Several disorders and diseases are discussed by covering the aforementioned biological processes. Structural features of galectin-7 are discussed as well as targeting the protein intracellularly or extracellularly. The exact molecular mechanisms that lie behind many biological processes involving galectin-7 are not known. It is therefore useful to come up with chemical probes or tools in order to obtain knowledge of the physiological processes. The objective of this review is to summarize the roles and functions of galectin-7 in the human body, providing reasons why it is necessary to design inhibitors for galectin-7, to give the reader structural insights and describe its current inhibitors.

Keywords: apoptosis; epithelial tissues; galectin-7; inhibitors; targeting.

Figure 1

(a) Dimeric structure of galectin-7 (pdb 1BKZ); (b) N-Ac-LacNAc binding to galectin-7 (pdb 5GAL).

Figure 2

Structures of 1 and 2: these two molecules differ by the presence of the O-benzylphosphate group in 2, compared with an O-methylphosphate group in 1.

Figure 3

Structures of 3 (Galβ1-3GlcNAc, LN1) and 4 (Galβ1-4GlcNAc, LN2).

Figure 4

Structures of 5, 6 and 7 (D1, D2 and D3, respectively).

Figure 4

Structures of 5, 6 and 7 (D1, D2 and D3, respectively).

Figure 5

Structure of 8 (TD139).

Figure 6

Structures of the scaffold 9 and the inhibitors 10 (K_d = 0.17 mM), 11 (K_d = 0.18 mM) and 12 (K_d = 0.14 mM).

Figure 7

Thioureido N-acetyllactosamine derivative 16.

Figure 8

Ditriazolylthio-digalactosides developed by Delaine et al.

Figure 9

Structure of a novel non-carbohydrate galectin-7 inhibitor 27 (TpSPPH₂).