Interactions between dodecamers of hyaluronan and hyaluronan-like molecules with TSG-6 protein

Kód výsledku v IS VaVaI

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Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Interactions between dodecamers of hyaluronan and hyaluronan-like molecules with TSG-6 protein

Popis výsledku v původním jazyce

Hyaluronan (HA) is a linear non-sulfated polysaccharide of natural origin, which contains disaccharide repeats of D-glucuronic acid and N-acetyl-D-glucosamine. HA is found pervasively in the extracellular matrix (ECM), where it can noncovalently bind to a variety of proteins and influence their functions. The biological functions of HA depend on the molecular weight of its chain [1]. One of the modified HA, hyaluronan neutral analog (GlcHA), where recurrent monosaccharide units of D-glucuronic acid from HA were substituted by D-glucose, can be promising biocompatible material for the design of drugs [2]. Tumor necrosis factor stimulated gene-6 (TSG-6) is a hyaluronan-binding protein (hyaladherin) that is essential for stabilizing and remodeling the ECM. This protein consists mainly contiguous N-terminal Link and C-terminal CUB domains, it is a potential biomarker of diseases associated with carcinogenesis, which is a possible target for drug delivery [3]. In this study, we simulated the binding of hyaluronan dodecamer (HA12) and its neutral analog (GlcHA12) to the Link domain of TSG-6 protein by using a molecular dynamics method. All simulations were performed in GROMACS software package (version 5.1.2) using the CHARMM36 all-atom force field at two different concentrations of NaCl solutions at 300 K under an NVT conditions. The ability of binding both HA12 and GlcHA12 seems to be facilitated by the high occurrence of the amino acids capable of hydrogen-bond formation, especially lysines and arginines, and the flexibility of the Link-domain structure allowing the protein to adapt to the ligand shape. It suggested the potentiality of designing synthetic ligands of protein receptors with regard to their possible pharmaceutical applications.

Název v anglickém jazyce

Interactions between dodecamers of hyaluronan and hyaluronan-like molecules with TSG-6 protein

Popis výsledku anglicky

Hyaluronan (HA) is a linear non-sulfated polysaccharide of natural origin, which contains disaccharide repeats of D-glucuronic acid and N-acetyl-D-glucosamine. HA is found pervasively in the extracellular matrix (ECM), where it can noncovalently bind to a variety of proteins and influence their functions. The biological functions of HA depend on the molecular weight of its chain [1]. One of the modified HA, hyaluronan neutral analog (GlcHA), where recurrent monosaccharide units of D-glucuronic acid from HA were substituted by D-glucose, can be promising biocompatible material for the design of drugs [2]. Tumor necrosis factor stimulated gene-6 (TSG-6) is a hyaluronan-binding protein (hyaladherin) that is essential for stabilizing and remodeling the ECM. This protein consists mainly contiguous N-terminal Link and C-terminal CUB domains, it is a potential biomarker of diseases associated with carcinogenesis, which is a possible target for drug delivery [3]. In this study, we simulated the binding of hyaluronan dodecamer (HA12) and its neutral analog (GlcHA12) to the Link domain of TSG-6 protein by using a molecular dynamics method. All simulations were performed in GROMACS software package (version 5.1.2) using the CHARMM36 all-atom force field at two different concentrations of NaCl solutions at 300 K under an NVT conditions. The ability of binding both HA12 and GlcHA12 seems to be facilitated by the high occurrence of the amino acids capable of hydrogen-bond formation, especially lysines and arginines, and the flexibility of the Link-domain structure allowing the protein to adapt to the ligand shape. It suggested the potentiality of designing synthetic ligands of protein receptors with regard to their possible pharmaceutical applications.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10610 - Biophysics

Projekt

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Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů