scholarly journals Microscale Thermophoresis Reveals Oxidized Glutathione as High-Affinity Ligand of Mal d 1

Foods ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2771
Author(s):  
Soraya Chebib ◽  
Wilfried Schwab
Keyword(s):  
Secondary Structure ◽  
Hydrophobic Interactions ◽  
Dissociation Constants ◽  
Physiological Role ◽  
Hydrophilic Interactions ◽  
Microscale Thermophoresis ◽  
Affinity Ligand ◽  
Pathogenesis Related ◽  
Mal D 1 ◽  
High Affinity Ligand

Pathogenesis-related (PR)-10 proteins, due to their particular secondary structure, can bind various ligands which could be important for their biological function. Accordingly, the PR-10 protein Mal d 1, the major apple allergen, probably also binds molecules in the hydrophobic cavity of its secondary structure, but it has not yet been investigated in this respect. In this study, various natural products found in apples such as flavonoids, glutathione (GSH), and glutathione disulfide (GSSG) were investigated as possible ligands of Mal d 1 using microscale thermophoresis. Dissociation constants of 16.39 µM, 29.51 µM, 35.79 µM, and 0.157 µM were determined for catechin, quercetin-3-O-rhamnoside, GSH, and GSSG, respectively. Molecular docking was performed to better understand the underlying binding mechanism and revealed hydrophobic interactions that stabilize the ligands within the pocket while hydrophilic interactions determine the binding of both GSH derivatives. The binding of these ligands could be important for the allergenicity of the PR-10 protein and provide further insights into its physiological role.

In-tandem insight from basic science combined with clinical research: CD38 as both marker and key component of the pathogenetic network underlying chronic lymphocytic leukemia

Blood ◽  
2006 ◽  
Vol 108 (4) ◽  
pp. 1135-1144 ◽  
Author(s):  
Silvia Deaglio ◽  
Tiziana Vaisitti ◽  
Semra Aydin ◽  
Enza Ferrero ◽  
Fabio Malavasi
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Prognostic Markers ◽  
Diagnostic Marker ◽  
Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Affinity Ligand ◽  
Survival Potential ◽  
Receptor Cross Talk ◽  
Indirect Confirmation ◽  
High Affinity Ligand

Abstract The absence of mutations in the IgV genes, together with the presence of ZAP-70 and CD38, are the most reliable negative prognostic markers for chronic lymphocytic leukemia (CLL) patients. Several lines of evidence indicate that CD38 may be not only a diagnostic marker but also a key element in the pathogenetic network in CLL. First, CD38 is a receptor that induces proliferation and increases survival of CLL cells. Second, CD38 signals start upon interaction with the CD31 ligand expressed by stromal and nurse-like cells. Third, CD38/CD31 contacts up-regulate CD100, a semaphorin involved in sustaining CLL growth. Fourth, evidence that nurselike cells express high levels of CD31 and plexin-B1, the high-affinity ligand for CD100, offers indirect confirmation for this model of receptor cross-talk. Elements of variation in the clinical course of CD38+ CLL patients include (1) potential intersection with ZAP-70, a kinase involved in the CD38 signaling pathway in T and natural killer (NK) cells, and (2) the effects of genetic polymorphisms of the receptors involved, at least of CD38 and CD31. Consequently, CD38 together with ZAP-70 appear to be the key elements of a coreceptor pathway that may sustain the signals mediated by the B-cell receptor and potentially by chemokines and their receptors. This would result in acquisition of increased survival potential, providing clues to the poorer prognosis of CD38+ patients.

scholarly journals A novel radioiodinated high affinity ligand for the D2 -dopamine receptor

FEBS Letters ◽  
1984 ◽  
Vol 176 (2) ◽  
pp. 436-440 ◽  
Author(s):  
Nourdine Amlaiky ◽  
Brian F. Kilpatrick ◽  
Marc G. Caron
Keyword(s):  
Dopamine Receptor ◽  
D2 Dopamine Receptor ◽  
High Affinity ◽  
Affinity Ligand ◽  
High Affinity Ligand

scholarly journals High-Affinity Ligand Probes of CD22 Overcome the Threshold Set bycisLigands to Allow for Binding, Endocytosis, and Killing of B Cells

2006 ◽  
Vol 177 (5) ◽  
pp. 2994-3003 ◽  
Author(s):  
Brian E. Collins ◽  
Ola Blixt ◽  
Shoufa Han ◽  
Bao Duong ◽  
Hongyi Li ◽  
...  
Keyword(s):  
B Cells ◽  
High Affinity ◽  
Affinity Ligand ◽  
High Affinity Ligand

scholarly journals RS-45041-190: a selective, high-affinity ligand for I2 imidazoline receptors

1995 ◽  
Vol 116 (2) ◽  
pp. 1737-1744 ◽  
Author(s):  
C.M. Brown ◽  
A.C. MacKinnon ◽  
W.S. Redfern ◽  
A. Williams ◽  
C. Linton ◽  
...  
Keyword(s):  
Imidazoline Receptors ◽  
High Affinity ◽  
Affinity Ligand ◽  
High Affinity Ligand

scholarly journals (De)stabilization of Alpha-Synuclein Fibrillary Aggregation by Charged and Uncharged Surfactants

2021 ◽  
Vol 22 (22) ◽  
pp. 12509
Author(s):  
Joana Angélica Loureiro ◽  
Stéphanie Andrade ◽  
Lies Goderis ◽  
Ruben Gomez-Gutierrez ◽  
Claudio Soto ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Hydrophobic Interactions ◽  
Neurodegenerative Disorder ◽  
Sodium Dodecyl ◽  
Lewy Bodies ◽  
Alpha Synuclein ◽  
Cetyltrimethylammonium Chloride ◽  
Α Helix ◽  
Β Sheet

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. An important hallmark of PD involves the pathological aggregation of proteins in structures known as Lewy bodies. The major component of these proteinaceous inclusions is alpha (α)-synuclein. In different conditions, α-synuclein can assume conformations rich in either α-helix or β-sheets. The mechanisms of α-synuclein misfolding, aggregation, and fibrillation remain unknown, but it is thought that β-sheet conformation of α-synuclein is responsible for its associated toxic mechanisms. To gain fundamental insights into the process of α-synuclein misfolding and aggregation, the secondary structure of this protein in the presence of charged and non-charged surfactant solutions was characterized. The selected surfactants were (anionic) sodium dodecyl sulphate (SDS), (cationic) cetyltrimethylammonium chloride (CTAC), and (uncharged) octyl β-D-glucopyranoside (OG). The effect of surfactants in α-synuclein misfolding was assessed by ultra-structural analyses, in vitro aggregation assays, and secondary structure analyses. The α-synuclein aggregation in the presence of negatively charged SDS suggests that SDS-monomer complexes stimulate the aggregation process. A reduction in the electrostatic repulsion between N- and C-terminal and in the hydrophobic interactions between the NAC (non-amyloid beta component) region and the C-terminal seems to be important to undergo aggregation. Fourier transform infrared spectroscopy (FTIR) measurements show that β-sheet structures comprise the assembly of the fibrils.

scholarly journals Therapeutic Targeting of the Gas6/Axl Signaling Pathway in Cancer

2021 ◽  
Vol 22 (18) ◽  
pp. 9953
Author(s):  
Mai Tanaka ◽  
Dietmar W. Siemann
Keyword(s):  
Signaling Pathway ◽  
Receptor Tyrosine Kinase ◽  
Therapeutic Agents ◽  
Therapeutic Interventions ◽  
Therapeutic Resistance ◽  
Clinical Settings ◽  
Affinity Ligand ◽  
Current State ◽  
Cancer Types ◽  
High Affinity Ligand

Many signaling pathways are dysregulated in cancer cells and the host tumor microenvironment. Aberrant receptor tyrosine kinase (RTK) pathways promote cancer development, progression, and metastasis. Hence, numerous therapeutic interventions targeting RTKs have been actively pursued. Axl is an RTK that belongs to the Tyro3, Axl, MerTK (TAM) subfamily. Axl binds to a high affinity ligand growth arrest specific 6 (Gas6) that belongs to the vitamin K-dependent family of proteins. The Gas6/Axl signaling pathway has been implicated to promote progression, metastasis, immune evasion, and therapeutic resistance in many cancer types. Therapeutic agents targeting Gas6 and Axl have been developed, and promising results have been observed in both preclinical and clinical settings when such agents are used alone or in combination therapy. This review examines the current state of therapeutics targeting the Gas6/Axl pathway in cancer and discusses Gas6- and Axl-targeting agents that have been evaluated preclinically and clinically.

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