Increased local production of PGD2 in skin lesions of patients with chronic spontaneous urticaria

Khanna, Shivani; Chichester, Kristin L.; Devine, Kelly; Gao, Peisong; Saini, Sarbjit S.; Oliver, E

doi:10.1016/j.jaci.2021.12.722

Cited by 2 publications

(1 citation statement)

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“…Inhibiting HPGDS is a potential strategy for modulating the production of PGD2 and its downstream effects, mainly resulting from inflammation [13,14]. Investigating the inhibitors is a way to cure PGD2-induced inflammation, such as allergic disorders, asthma, sleep disorders, chronic spontaneous urticarial, and hair loss [15][16][17][18]. Studies have been conducted to investigate HPGDS inhibitors, and several commercially available compounds, including HQL-79 [19], TFC-007 [20], and TAS-204 [21], were recognized as HPGS inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Computer-Aided Designing Peptide Inhibitors of Human Hematopoietic Prostaglandin D2 Synthase Combined Molecular Docking and Molecular Dynamics Simulation

et al. 2023

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Human hematopoietic prostaglandin D2 synthase (HPGDS) is involved in the production of prostaglandin D2, which participates in various physiological processes, including inflammation, allergic reactions, and sleep regulation. Inhibitors of HPGDS have been investigated as potential anti-inflammatory agents. For the investigation of potent HPGDS inhibitors, we carried out a computational modeling study combining molecular docking and molecular dynamics simulation for selecting and virtual confirming the designed binders. We selected the structure of HPGDS (PDB ID: 2CVD) carrying its native inhibitor compound HQL as our research target. The random 5-mer peptide library was created by building the 3-D structure of random peptides using Rosetta Buildpeptide and performing conformational optimization. Molecular docking was carried out by accommodating the peptides into the location of their native binder and then conducting docking using FlexPepDock. The two peptides RMYYY and VMYMI, which display the lowest binding energy against HPGDS, were selected to perform a comparative study. The interaction of RMYYY and VMYMI against HPGDS was further confirmed using molecular dynamics simulation and aligned with its native binder, HQL. We show the selected binders to have stronger binding energy and more frequent interactions against HPGDS than HQL. In addition, we analyzed the solubility, hydrophobicity, charge, and bioactivity of the generated peptides, and we show that the selected strong binder may be further used as therapeutic drugs.

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