Galectin

About: Galectin is a research topic. Over the lifetime, 2076 publications have been published within this topic receiving 103409 citations. The topic is also known as: IPR001079 & Galectin.

Chicken lens development: complete signature of expression of galectins during embryogenesis and evidence for their complex formation with α-, β-, δ-, and τ-crystallins, N-CAM, and N-cadherin obtained by affinity chromatography

Abstract: The emerging multifunctionality of galectins by specific protein-glycan/protein interactions explains the interest to determine their expression during embryogenesis. Complete network analysis of all seven chicken galectins (CGs) is presented in the course of differentiation of eye lens that originates from a single type of progenitor cell. It answers the questions on levels of expression and individual patterns of distribution. A qualitative difference occurs in the CG-1A/B paralogue pair, underscoring conspicuous divergence. Considering different cell phenotypes, lens fiber and also epithelial cells can both express the same CG, with developmental upregulation for CG-3 and CG-8. Except for expression of the lens-specific CG (C-GRIFIN), no other CG appeared to be controlled by the transcription factors L-Maf and Pax6. Studying presence and nature of binding partners for CGs, we tested labeled galectins in histochemistry and in ligand blotting. Mass spectrometric (glyco)protein identification after affinity chromatography prominently yielded four types of crystallins, N-CAM, and, in the cases of CG-3 and CG-8, N-cadherin. Should such pairing be functional in situ, it may be involved in tightly packing intracellular lens proteins and forming membrane contact as well as in gaining plasticity and stability of adhesion processes. The expression of CGs throughout embryogenesis is postulated to give meaning to spatiotemporal alterations in the local glycome.

Synthetic Inhibitors of Galectins: Structures and Syntheses

Abstract: The recent discovery of the critical involvement of galectins in cancer progression, and in inflammatory and immune responses, has raised this family of β-D-galactoside-binding proteins to the rank of high-priority drug targets by the scientific community. This report will highlight the relevance of glycochemistry toward the efficient development of synthetic galectins inhibitors with high affinity and selectivity, as small molecules or multivalent glycoconjugates. A. Introduction Lectins are carbohydrate-binding proteins that are grouped into several families (1, 2). Among them, galectins (15 mammalian members identified to date) share a consensus amino acid sequence and are recognized for their ability to bind β-galactoside residues (3, 4). Natural ligands of galectins are N-acetyl lactosamine, lactose and any glycoconjugates with a non-reducing galactoside terminus. The most striking features of galectins are their ability to regulate numerous biological processes (5), including an active involvement in a number of cellular events including neoplastic transformation, tumor cell survival processes, angiogenesis and tumor metastasis (6, 7). They are also known to regulate important cell phenomena that are critical for immune cell homeostasis (8– 10). Their functions are directly related to the ability of galectins to cross-link glycoconjugates harboring multiple galactopyranoside residues (11). This phenomenon can be explained by the fact that galectins can assemble in three different and specific architectures, i.e., proto-type, tandem repeat-type, and chimera-type (12). This diversity opens the door for the exploration of a myriad of structural combinations in the quest for the synthesis of potent and optimized inhibitors. Consequently, the scientific community recently directed efforts toward synthetic compounds having high affinities with galectins with the aim of deciphering their biological roles. Synthetic strategies to prepare galectin inhibitors have already been nicely summarized in reviews by the groups of Nilsson (13, 14), Mayo (15), Pieters (16), and Kiss (17).To complement these reports, we wish to shed some light on the synthetic pathways specifically leading to sugar-based inhibitors, emphasizing a comprehensive analysis of their chemical structures that is required to properly identify potential clinical candidates. In that purpose and in the interest of clarity, different structural families including monosaccharides, disaccharides, glycoclusters and glycodendrimers will be described separately. It is noteworthy that combinatorial peptide (18) or glycopeptide (19) libraries will not be covered in this review. B. Structural Features of Galectins Galectins contain conserved carbohydrate recognition domain (CRD) of about 135 amino acids (20). For human galectin-3, eight amino acids (Arg144, His158, Asn160, Arg162, Arg186, Asn174, Trp181, and Glu184) interact with the carbohydrate. Considering the fact that the glycan binding site is described by five subsites A–E (21, 22), the galactose residue of lactose binds in subsite C, while subsite D accommodates the glucose moiety. Fig. 1 summarizes key features of the galectin–carbohydrate interactions based on the X-ray structure of galectin complexed to lactose (PDB 2NN8) (23) and allows the rationalization of the potential chemical functionalizations that can be realized toward the synthesis of optimized ligands. It is important to point out that if the 2-OH group on the glucose residue is replaced with an acetamide (LacNAc as ligand), similar interactions are possible with Arg186. i) The endocyclic oxygen of the galactose residue directly hydrogen bonds with Arg162; ii) 3′-OH group interacts indirectly with Arg144 via a water molecule; iii) 4′-OH has hydrogen bonding interactions directly with His158, Asn160, Arg162 and indirectly with Arg144 by the MINIREVIEW doi: 10.4052/tigg.1729.1SE Fig. 1. Interactions between lactose and the CRD amino acids of galectin-3. Subsite C encloses the galactose residue and subsite D encloses the glucose residue. Dotted lines denote hydrogen bonding. (Article for special issue on Galectins)