Identification and evaluation of glutathione conjugate gamma-<scp>l</scp>-glutamyl-<scp>l</scp>-cysteine for improved drug delivery to the brain

Fatima, Saman; Mohammad, Taj; Jairajpuri, Deeba Shamim; Rehman, Tabish; Hussain, Afzal; Samim, Mohammed; Ahmad, Feroz; Alajmi, Mohamed F.; Hassan, Md. Imtaiyaz

doi:10.1080/07391102.2019.1664937

Cited by 51 publications

(26 citation statements)

References 53 publications

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“…The concept has been specifically applied to an anti-Aβ amyloid VHH after encapsulation in liposomes decorated with glutathione (GSH) [ 58 ]. This tripeptide was believed to use a specific carrier that was recently reported to be the N-Methyl-D-Aspartate receptor (NMDAR) [ 59 ]. This VHH pa2H encapsulated into liposomes was able to stain amyloid plaques into the brain after intravenous administration.…”

Section: Single-domain Antibodies Crossing the Blood–brain Barriermentioning

confidence: 99%

Brain Delivery of Single-Domain Antibodies: A Focus on VHH and VNAR

2020

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Passive immunotherapy, i.e., treatment with therapeutic antibodies, has been increasingly used over the last decade in several diseases such as cancers or inflammation. However, these proteins have some limitations that single-domain antibodies could potentially solve. One of the main issues of conventional antibodies is their limited brain penetration because of the blood–brain barrier (BBB). In this review, we aim at exploring the different options single-domain antibodies (sDAbs) such as variable domain of heavy-chain antibodies (VHHs) and variable new antigen receptors (VNARs) have already taken to reach the brain allowing them to be used as therapeutic, diagnosis or transporter tools.

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Section: Single-domain Antibodies Crossing the Blood–brain Barriermentioning

confidence: 99%

Brain Delivery of Single-Domain Antibodies: A Focus on VHH and VNAR

2020

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“…Any small molecule can induce a large conformational change in a protein after binding [26][27][28][29]. Root-mean-square deviation (RMSD) is an important approach to estimate the structural deviation and stability of a protein structure [30][31][32][33][34][35].…”

Section: Structural Deviation and Compactnessmentioning

confidence: 99%

Identification of High-Affinity Inhibitors of Cyclin-Dependent Kinase 2 Towards Anticancer Therapy

et al. 2019

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Cyclin-dependent kinase 2 (CDK2) is an essential protein kinase involved in the cell cycle regulation. The abnormal activity of CDK2 is associated with cancer progression and metastasis. Here, we have performed structure-based virtual screening of the PubChem database to identify potent CDK2 inhibitors. First, we retrieved all compounds from the PubChem database having at least 90% structural similarity with the known CDK2 inhibitors. The selected compounds were subjected to structure-based molecular docking studies to investigate their pattern of interaction and estimate their binding affinities with CDK2. Selected compounds were further filtered out based on their physicochemical and ADMET properties. Detailed interaction analysis revealed that selected compounds interact with the functionally important residues of the active site pocket of CDK2. All-atom molecular dynamics simulation was performed to evaluate conformational changes, stability and the interaction mechanism of CDK2 in-complex with the selected compound. We found that binding of 6-N,6-N-dimethyl-9-(2-phenylethyl)purine-2,6-diamine stabilizes the structure of CDK2 and causes minimal conformational change. Finally, we suggest that the compound (PubChem ID 101874157) would be a promising scaffold to be further exploited as a potential inhibitor of CDK2 for therapeutic management of cancer after required validation.

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“…Molecular dynamics studies are generated using the software GROMAS version 4.5.5 [ 55 ], Molecular dynamics (MD) simulation has been a significant part used to assess the structural dynamics of protein-ligand complex and their structural stability under solvent system [ 56 , 57 ]. In this study, MD simulations were carried out for a timescale of 50 ns using the interaction of the protein-ligand complex.…”

Section: Molecular Dynamics Studiesmentioning

confidence: 99%

Exploring the molecular structure, vibrational spectroscopic, quantum chemical calculation and molecular docking studies of curcumin: A potential PI3K/AKT uptake inhibitor

Govindammal

Prasath

Kamaraj

et al. 2021

Heliyon

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The IUPAC name of curcumin is (1E, 6E)-1,7-Bis(4-hydroxy-3methoxyphenyl) hepta-1,6-e-3,5-dione (7B3M5D) and is characterized by spectroscopic profiling with FT-IR and FT-Raman spectra obtained both experimentally and theoretically. PED analysis was done for the confirmation of minimum energy obtained in the title compound. Optimized geometrical parameters are compared with experimental values obtained for 7B3M5D by utilizing B3LYP functional employing 6–311++G (d,p) level of theory. The HOMO-LUMO, MEP, and Fukui function analysis has been used to elucidate the information regarding charge transfer within the molecule. The stabilization energy and charge delocalization of the 7B3M5D were performed by NBO analysis. This article assesses that the title compound act as a potential inhibitor of the PI3K/AKT inhibitor through in silico studies, like molecular docking, molecular dynamics (MD), ADMET prediction and also this molecule obeys Lipinski's rule of five. 7B3M5D was docked effectively in the active site of PI3K/AKT inhibitor.

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Identification and evaluation of glutathione conjugate gamma-l-glutamyl-l-cysteine for improved drug delivery to the brain

Cited by 51 publications

References 53 publications

Brain Delivery of Single-Domain Antibodies: A Focus on VHH and VNAR

Brain Delivery of Single-Domain Antibodies: A Focus on VHH and VNAR

Identification of High-Affinity Inhibitors of Cyclin-Dependent Kinase 2 Towards Anticancer Therapy

Exploring the molecular structure, vibrational spectroscopic, quantum chemical calculation and molecular docking studies of curcumin: A potential PI3K/AKT uptake inhibitor

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