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A Synthetic Heparin Mimetic that Allosterically Inhibits Factor XIa and Reduces Thrombosis In Vivo without Enhanced Risk of Bleeding.
No full textBackground: Human factor XIa (FXIa) is an actively pursued target for development of safer anticoagulants. Our long-standing hypothesis has been that allosterism originating from heparin-binding site(s) on coagulation enzymes is a promising approach to yield safer agents. Objectives: To develop a synthetic heparin mimetic as an inhibitor of FXIa so as to reduce clot formation in vivo but not carry high bleeding risk. Methods: We employed a gamut of methods involving synthetic chemistry, biophysical biochemistry, enzyme assays, blood and plasma coagulation assays, and in vivo thrombosis models in this work. Results: Sulfated chiro-inositol (SCI), a non-saccharide mimetic of heparin, was synthesized in three steps in overall yields of \u3e50%. SCI inhibited FXIa with potency of 280 nmol/L and preferentially engaged FXIa\u27s heparin-binding site to conformationally alter its active site. SCI inhibition of FXIa could be rapidly reversed by common antidotes, such as protamine. SCI preferentially prolonged plasma clotting initiated with recalcification, rather than thromboplastin, alluding to its intrinsic pathway-based mechanism. Human blood thromboelastography indicated good ex vivo anticoagulation properties of SCI. Rat tail bleeding and maximum-dose-tolerated studies indicated that no major bleeding or toxicity concerns for SCI suggesting a potentially safer anticoagulation outcome. FeCl3-induced arterial and thromboplastin-induced venous thrombosis model studies in the rat showed reduced thrombus formation by SCI at 250 μg/animal, which matched enoxaparin at 2500 μg/animal. Conclusions: Overall, SCI is a highly promising, allosteric inhibitor of FXIa that induces potent anticoagulation in vivo. Further studies are necessary to assess SCI in animal models mimicking human clinical indications
Xavier University Library Collections Newsletter Volume 1 Issue 2
Get PDFThe Smithsonian Institute has borrowed Xavier University of Louisiana Library’s photograph of Mrs. Margaret James Washington for an exhibition at the National Portrait Gallery. Mrs. Washington was an anti-lynching activist in the late 1800s and the first “lady principal” at what is today Tuskegee University. The exhibit, “Votes for Women: A Portrait of Persistence,” will reveal the women and organizations often overlooked in the complex narrative of women’s suffrage.https://digitalcommons.xula.edu/archives_newsletter/1001/thumbnail.jp
The pedagogy of design and technology at Xavier University of Louisiana, New Orleans
Get PDFAbstract. Xavier University of Louisiana (XULA) is a Science, Technology, Engineering, and Mathematics (STEM) university located in New Orleans, Louisiana. As a Historically Black University (HBCU), the university serves a diverse community of students in which many are first-generation, college graduates. Students enrolled in Design courses at XULA are studying in Bachelor of Science and Bachelor of Art programs and majoring in subjects such as Computer Science, Physics, Mass Communication, Art, Business, and Science. The interdisciplinary student environment offers a unique opportunity for collaboration and peer learning, whereby students are able to share diverse perspectives on a topic by relating design processes to their fields of study. In laboratory practice, students work on independent and collaborative projects in Product Design and User Experience by developing work through a design process from ideation to production
Organic Chemistry I Drill (CHEM2210D)-3rd Module-Sample B- Answer Key
No full textThis module teaches Resonace, Using curved arrows and Acid-base reaction
Organic Chemistry I Drill (CHEM2210D) - Module 10- Sample B. Answer Key
Get PDFThis module deals with free radical reactions and polymers
Organic Chemistry II Drill (CHEM2220D). Module 8. Sample B. Answer keys
Get PDFThis module deals with alpha Carbon Chemistry; enols and enolate