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.

Synthetic Galectin Inhibitors Selective O-galactosyl aldoximes, multivalent lactosides and galactose-mimicking mannosides

Abstract: This thesis describes the design, synthesis and evaluation of synthetic inhibitors for the carbohydrate binding proteins called galectins. Potent and selective inhibitors can be used as important research tools in the endeavor to chart the true role of galectins in biological events such as cancer and inflammation and possibly as lead for future galectin targeting drugs. A panel of O-galactosyl aldoximes was synthesized and inhibitors with high affinity and selectivity for galectin-3 and -7 were identified. The best inhibitor for galectin-3, O-(?-D-galactopyranosyl)-indole-3-carbaldoxime, was combined with previously optimized galectin-3 targeting triazoles, in a fragment based approach, to give 3C-triazol-1-yl-O-galactopyranosyl aldoximes with high affinity and selectivity for galectin-3 (Kd down to 11 µM). Furthermore, a glycoside clustering effect was observed for multivalent lactose containing inhibitors and galectin-1. The mechanisms behind this were investigated using mutated galectin-1, lacking the possibility to dimerize. Finally, 1H-[1,2,3]-triazol-1-yl mannosides, with synthetic advantages over galactose based inhibitors, were synthesized and the 4-benzylaminocarbonyl-1H-[1,2,3]-triazol-1-yl ?-D-mannopyranoside (Kd=540 µM, for galectin-9N) compared favorably with its galactoside counterpart.

Serum Galectin 7 is Not Useful to Predict Abortion in the First Trimester.

Abstract: Objective: Galectins are animal lectins that bind to surface glycoproteins expressed at the fetal-maternal interface. The aim of this prospective case–control study was to investigate the possible ...

Evaluating the affinity and kinetics of small molecule glycomimetics for human and mouse galectin-3 using surface plasmon resonance.

Abstract: Galectin-3 is a beta-galactoside-binding mammalian lectin that is one of a 15-member galectin family that can bind several cell surface glycoproteins via its carbohydrate recognition domain (CRD). As a result, it can influence a range of cellular processes including cell activation, adhesion and apoptosis. Galectin-3 has been implicated in various diseases, including fibrotic disorders and cancer, and is now being therapeutically targeted by both small and large molecules. Historically, the screening and triaging of small molecule glycomimetics that bind to the galectin-3 CRD has been completed in fluorescence polarisation (FP) assays to determine KD values. Surface plasmon resonance (SPR) has not been widely used for compound screening and in this study it was used to compare human and mouse galectin-3 affinity measures between FP and SPR, as well as investigate compound kinetics. The KD estimates for a set of compounds selected from mono- and di-saccharides with affinities across a 550-fold range, correlated well between FP and SPR assay formats for both human and mouse galectin-3. Increases in affinity for compounds binding to human galectin-3 were driven by changes in both kon and koff whilst for mouse galectin-3 this was primarily due to kon. The reduction in affinity observed between human to mouse galectin-3 was also comparable between assay formats. SPR has been shown to be a viable alternative to FP for early drug discovery screening and determining KD values. In addition, it can also provide early kinetic characterisation of small molecule galectin-3 glycomimetics with robust kon and koff values generated in a high throughput manner.

Galectins as targets for angiostatic cancer therapy

Abstract: Approximately 30-40% of the patients with early stage non-small cell lung cancer (NSCLC) will present with recurrent disease within two years of resection. Here, we performed extensive galectin expression profi ling in a retrospective study using frozen and paraffi n embedded tumor tissues from 87 stage I/II NSCLC patients. Our data show that galectin mRNA expression in NSCLC is confi ned to galectin-1,-3,-4,-7,-8, and -9. Next to stage, univariable Cox regression analysis identifi ed galectin-1, galectin-9FL and galectin-9∆5 as possible prognostic markers. KaplanMeier survival estimates revealed that overall survival was signifi cantly shorter in patients that express galectin-1 above median levels, i.e. 23.0 (2.9-43.1) vs. 59.9 (47.7-72.1) months (p=0.020) as well as in patients that express galectin-9∆5 or galectin-9FL below the median, resp. 59.9 (41.9-75.9) vs. 32.8 (8.7-56.9) months (p=0.014) or 23.2 (-0.4-46.8) vs. 58.9 (42.9-74.9) months (p=0.042). All three galectins were also prognostic for disease free survival. Multivariable Cox regression analysis showed that for OS, the most signifi cant prognostic model included stage, age, gal-1 and gal-9∆5 while the model for DFS included stage, age and gal-9∆5. In conclusion, the current study confi rms the prognostic value of galectin-1 and identifi es galectin-9∆5 as a novel potential prognostic marker in early stage NSCLC. These fi ndings could help to identify early stage NSCLC patients that might benefi t most from adjuvant chemotherapy.

Trim proteins and galectins cooperate and codirect autophagy and are useful in the treatment of autophagy related diseases

Abstract: Tie present invention relates to compositions and methods of influencing autophagy by modulating TRIM (tripartite motif containing) proteins, especially TRIM 8, TRIM: 10, TRIM 16, TRIM 19 and/or TRI.M 51 (preferably TRIM 16} and galectins, especially galectins 3 m order to influence authophagy and treat a number of disease states and/or conditions which are mediated and/or influenced by autophagy, including inflammatory disease states and/or conditions, including a microbial infection such as a Mycobacterium infection, among numerous others, an inflammatory disorder, a lysosomal, storage disorder, an immune disorder, a neurodegenerative disorder and a cancer.