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Medicinal-Pharmaceutical Chemistry Commons™
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Articles 1 - 3 of 3
Full-Text Articles in Medicinal-Pharmaceutical Chemistry
End-Point Modification Of Recombinant Thrombomodulin With Enhanced Stability And Anticoagulant Activity, Xia Liu, Mallorie Boron, Yu Zhao, Xue-Long Sun
End-Point Modification Of Recombinant Thrombomodulin With Enhanced Stability And Anticoagulant Activity, Xia Liu, Mallorie Boron, Yu Zhao, Xue-Long Sun
Chemistry Faculty Publications
Thrombomodulin (TM) is an endothelial cell membrane protein that plays essential roles in controlling vascular haemostatic balance. The 4, 5, 6 EGF-like domain of TM (TM456) has cofactor activity for thrombin binding and subsequently protein C activation. Therefore, recombinant TM456 is a promising anticoagulant candidate but has a very short half-life. Ligation of poly (ethylene glycol) to a bioactive protein (PEGylation) is a practical choice to improve stability, extend circulating life, and reduce immunogenicity of the protein. Site-specific PEGylation is preferred as it could avoid the loss of protein activity resulting from nonspecific modification. We report herein …
A Quantitative Lc-Ms/Ms Method For Determination Of A Small Molecule Agonist Of Epha2 In Mouse Plasma And Brain Tissue, Bo Zhong, Yaxin Li, Nethrie Idippily, Aaron Petty, Bin Su Ph.D., Bingcheng Wang
A Quantitative Lc-Ms/Ms Method For Determination Of A Small Molecule Agonist Of Epha2 In Mouse Plasma And Brain Tissue, Bo Zhong, Yaxin Li, Nethrie Idippily, Aaron Petty, Bin Su Ph.D., Bingcheng Wang
Chemistry Faculty Publications
Compound 27 {1, 12‐bis[4‐(4‐amino‐6,7‐dimethoxyquinazolin‐2‐yl)piperazin‐1‐yl]dodecane‐1,12‐dione} is a novel small molecule agonist of EphA2 receptor tyrosine kinase. It showed much improved activity for the activation of EphA2 receptor compared with the parental compound doxazosin. To support further pharmacological and toxicological studies of the compound, a method using liquid chromatography and electrospray ionization tandem mass spectrometry (LC–MS/MS) has been developed for the quantification of this compound. Liquid–liquid extraction was used to extract the compound from mouse plasma and brain tissue homogenate. Reverse‐phase chromatography with gradient elution was performed to separate compound 27 from the endogenous molecules in the matrix, followed by …
Tracking Decitabine Incorporation Into Malignant Myeloid Cell Dna In Vitro And In Vivo By Lc-Ms/Ms With Enzymatic Digestion, Sujatha Chilakala, Ye Feng, Lan Li, Reda Mahfouz, Ebrahem Quteba, Yogen Saunthararajah, Yan Xu
Tracking Decitabine Incorporation Into Malignant Myeloid Cell Dna In Vitro And In Vivo By Lc-Ms/Ms With Enzymatic Digestion, Sujatha Chilakala, Ye Feng, Lan Li, Reda Mahfouz, Ebrahem Quteba, Yogen Saunthararajah, Yan Xu
Chemistry Faculty Publications
The DNA hypomethylating agents decitabine and 5-azacytidine are the only two drugs approved for treatment of all subtypes of the myeloid malignancy myelodysplastic syndromes (MDS). The key to drug activity is incorporation into target cell DNA, however, a practical method to measure this incorporation is un-available. Here, we report a sensitive and specific LC-MS/MS method to simultaneously measure decitabine incorporation and DNA hypomethylation. A stable heavy isotope of 2'-deoxycytidine was used as an internal standard and one-step multi-enzyme digestion was used to release the DNA bound drug. Enzyme-released decitabine along with other mononucleosides were separated by a reverse-phase C-18 column …