排序方式: 共有3条查询结果,搜索用时 15 毫秒
1
1.
Class II major histocompatibility complex (MHC II) molecules as expressed by antigen-presenting cells are heterodimeric cell-surface
glycoprotein receptors that are fundamental in initiating and propagating an immune response by presenting tumor-associated
antigenic peptides to CD4+/TH cells. The loading efficiency of such peptides can be improved by small organic compounds (MHC Loading Enhancers—MLEs), that
convert the non-receptive peptide conformation of MHC II to a peptide-receptive conformation. In a reversible reaction, these
compounds open up the binding site of MHC II molecules by specific interactions with a yet undefined pocket. Here, we performed
molecular docking and molecular dynamics simulation studies of adamantyl compounds on the predicted cavity around the P1 pocket
of 2 allelic variants of HLA-DRs. The purpose was to investigate the suitability of adamantyl compounds as MLEs at the dimorphic
β86 position. Docking studies revealed that besides numerous molecular interactions formed by the adamantyl compounds, Asnβ82,
Tyrβ83, and Thrβ90 are the crucial amino acid residues that are characterized as the “sensors” of peptide loading. Molecular
dynamics simulation studies exposed the dynamical structural changes that HLA-DRs adopted as a response to binding of 3-(1-adamantyl)-5-hydrazidocarbonyl-1H-pyrazole
(AdCaPy). The conformations of AdCaPy complexed with the Glyβ86 HLA-DR allelic variant are well correlated with the stabilized
form of peptide-loaded HLA-DRs, further confirming the role of AdCaPy as a MLE. Hydrogen bonding interaction analysis clearly
demonstrated that after making suitable contacts with AdCaPy, HLA-DR changes its local conformation. However, AdCaPy complexed
with HLA-DR having Valβ86 at the dimorphic position did not accommodate AdCaPy as MLE due to steric hindrance caused by the
valine. 相似文献
2.
Khalid M. Khan Nida Ambreen Muhammad Taha Sobia A. Halim Zaheer-ul-Haq Shagufta Naureen Saima Rasheed Shahnaz Perveen Sajjad Ali Mohammad Iqbal Choudhary 《Journal of computer-aided molecular design》2014,28(5):577-585
Using structure-based virtual screening approach, a coumarin derivative (1) was identified as β-glucuronidase inhibitor. A focused library of coumarin derivatives was synthesized by eco-benign version of chemical reaction, and all synthetic compounds were characterized by using spectroscopy. These compounds were found to be inhibitor of β-glucuronidase with IC50 values in a micromolar range. All synthetic compounds exhibited interesting inhibitory activity against β-glucuronidase, however, their potency varied substantially from IC50 = 9.9–352.6 µM. Of twenty-one compounds, four exhibited a better inhibitory profile than the initial hit 1. Interestingly, compounds 1e, 1k, 1n and 1p exhibited more potency than the standard inhibitor with IC50 values 34.2, 21.4, 11.7, and 9.9 µM, respectively. We further studied their dose responses and also checked our results by using detergent Triton ×-100. We found that our results are true and not affected by detergent. 相似文献
3.
Atta-ur-Rahman Feroz F Zaheer-ul-Haq Nawaz SA Khan MR Choudhary MI 《Natural product research》2003,17(4):235-241
Two new steroidal alkaloids, salonine-A [(20S)-20-(N,N-dimethylamino)-3beta-(tigloylamino)-5alpha-pregn-14-en-2beta,4beta-diol] (1), and salonine-B [(20S)-20-(N,N-dimethylamino)-3beta-methoxy-pregn-5,16-diene] (2), were isolated from the MeOH extract of Sarcococca saligna, along with a known base, alkaloid-C (3). Their structures were elucidated on the basis of spectroscopic methods. All three compounds were found to be cholinesterase inhibitors. 相似文献
1