This dissertation primarily focuses on how differences in molecular weight (MW) and structural composition affect the pharmacological activity of heparin and its derivatives. Heparins are a mixture of glycosaminoglycans chains which are used to prevent thrombosis in a number of clinical indications. Heparins promote the inhibition of blood coagulation via their plasmatic cofactors antithrombin (AT) and heparin cofactor II (HCII).
In these studies, various heparins with molecular weights ranging from 2.6 to 16.5 kDa were investigated. Not only the molecular weight but also the oligosaccharide composition greatly varied in these agents. One of the major objectives of this research was to investigate the pharmacological actions of a novel ultra low molecular weight heparin (ULMWH), namely semuloparin (AVE5026) and compare it with routinely used unfractionated heparin (UF) and the low molecular weight heparins (LMWH), enoxaparin and bemiparin. In addition, RO-14, another ULMWH, was studied for comparison. Semuloparin is currently in clinical development for the prevention of venous thromboembolism. Semuloparin is prepared by a highly selective depolymerization of the heparin backbone by a phosphazene base which preserves the antithrombin (AT) binding sequence. The unique structural features of semuloparin differentiate it from LMWHs. Unlike other depolymerized heparins where theantithrombin (AT) affinity components and anti-Xa activity is decreased with the decrease in the molecular weight, semuloparin exhibits a relatively higher proportion of AT-binding components which translates into a higher anti-Xa activity.
In conclusion, this dissertation clearly demonstrates that different MW and affinity profiles of UF, LMW, and ULMW heparins contribute to the unique pharmacological effects of these agents. In addition, these studies illustrate that heparins enrichment with the high-affinity AT binding sequences, which results in a higher anti-FXa/FIIa ratio, promotes a better antithrombotic and safety profile compared to non-enriched heparin derivatives. Overall, this dissertation provides a comprehensive biochemical and pharmacological investigation in which not only the molecular weight dependence, but also the differences in structural composition of heparin and its derivatives were determined.
","abstract_html":"<p>This dissertation primarily focuses on how differences in molecular weight (MW) and structural composition affect the pharmacological activity of heparin and its derivatives. Heparins are a mixture of glycosaminoglycans chains which are used to prevent thrombosis in a number of clinical indications. Heparins promote the inhibition of blood coagulation via their plasmatic cofactors antithrombin (AT) and heparin cofactor II (HCII).</p><p>In these studies, various heparins with molecular weights ranging from 2.6 to 16.5 kDa were investigated. Not only the molecular weight but also the oligosaccharide composition greatly varied in these agents. One of the major objectives of this research was to investigate the pharmacological actions of a novel ultra low molecular weight heparin (ULMWH), namely semuloparin (AVE5026) and compare it with routinely used unfractionated heparin (UF) and the low molecular weight heparins (LMWH), enoxaparin and bemiparin. In addition, RO-14, another ULMWH, was studied for comparison. Semuloparin is currently in clinical development for the prevention of venous thromboembolism. Semuloparin is prepared by a highly selective depolymerization of the heparin backbone by a phosphazene base which preserves the antithrombin (AT) binding sequence. The unique structural features of semuloparin differentiate it from LMWHs. Unlike other depolymerized heparins where theantithrombin (AT) affinity components and anti-Xa activity is decreased with the decrease in the molecular weight, semuloparin exhibits a relatively higher proportion of AT-binding components which translates into a higher anti-Xa activity.</p><p>In conclusion, this dissertation clearly demonstrates that different MW and affinity profiles of UF, LMW, and ULMW heparins contribute to the unique pharmacological effects of these agents. In addition, these studies illustrate that heparins enrichment with the high-affinity AT binding sequences, which results in a higher anti-FXa/FIIa ratio, promotes a better antithrombotic and safety profile compared to non-enriched heparin derivatives. Overall, this dissertation provides a comprehensive biochemical and pharmacological investigation in which not only the molecular weight dependence, but also the differences in structural composition of heparin and its derivatives were determined.</p>","abstract_has_math":false,"creators":["Gray-Shah, Angel Lee"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Educational Psychology","degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012-01-01T08:00:00Z","date_published":"2012-01-01T08:00:00Z","updated_at":"2026-07-24T02:55:31Z","subjects":["antithrombotic","cancer","low molecular weight heparins","semuloparin","ultra low molecular weight heparins","unfractionated heparins","Pharmacology"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://ecommons.luc.edu/luc_diss/411","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Gray-Shah, Angel Lee"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["1970-01-01T11:35:24Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Educational Psychology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["antithrombotic","cancer","low molecular weight heparins","semuloparin","ultra low molecular weight heparins","unfractionated heparins","Pharmacology"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://ecommons.luc.edu/luc_diss/411"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["This dissertation primarily focuses on how differences in molecular weight (MW) and structural composition affect the pharmacological activity of heparin and its derivatives. Heparins are a mixture of glycosaminoglycans chains which are used to prevent thrombosis in a number of clinical indications. Heparins promote the inhibition of blood coagulation via their plasmatic cofactors antithrombin (AT) and heparin cofactor II (HCII).
In these studies, various heparins with molecular weights ranging from 2.6 to 16.5 kDa were investigated. Not only the molecular weight but also the oligosaccharide composition greatly varied in these agents. One of the major objectives of this research was to investigate the pharmacological actions of a novel ultra low molecular weight heparin (ULMWH), namely semuloparin (AVE5026) and compare it with routinely used unfractionated heparin (UF) and the low molecular weight heparins (LMWH), enoxaparin and bemiparin. In addition, RO-14, another ULMWH, was studied for comparison. Semuloparin is currently in clinical development for the prevention of venous thromboembolism. Semuloparin is prepared by a highly selective depolymerization of the heparin backbone by a phosphazene base which preserves the antithrombin (AT) binding sequence. The unique structural features of semuloparin differentiate it from LMWHs. Unlike other depolymerized heparins where theantithrombin (AT) affinity components and anti-Xa activity is decreased with the decrease in the molecular weight, semuloparin exhibits a relatively higher proportion of AT-binding components which translates into a higher anti-Xa activity.
In conclusion, this dissertation clearly demonstrates that different MW and affinity profiles of UF, LMW, and ULMW heparins contribute to the unique pharmacological effects of these agents. In addition, these studies illustrate that heparins enrichment with the high-affinity AT binding sequences, which results in a higher anti-FXa/FIIa ratio, promotes a better antithrombotic and safety profile compared to non-enriched heparin derivatives. Overall, this dissertation provides a comprehensive biochemical and pharmacological investigation in which not only the molecular weight dependence, but also the differences in structural composition of heparin and its derivatives were determined.
"]},{"key":"dc:title","label":"Title","values":["Compositional Determinants of the Pharmacological Actions of Heparins"]}]}],"canonical_facts":{"dc:creator":["Gray-Shah, Angel Lee"],"dc:date.available":["1970-01-01T11:35:24Z"],"dc:description.abstract":["This dissertation primarily focuses on how differences in molecular weight (MW) and structural composition affect the pharmacological activity of heparin and its derivatives. Heparins are a mixture of glycosaminoglycans chains which are used to prevent thrombosis in a number of clinical indications. Heparins promote the inhibition of blood coagulation via their plasmatic cofactors antithrombin (AT) and heparin cofactor II (HCII).
In these studies, various heparins with molecular weights ranging from 2.6 to 16.5 kDa were investigated. Not only the molecular weight but also the oligosaccharide composition greatly varied in these agents. One of the major objectives of this research was to investigate the pharmacological actions of a novel ultra low molecular weight heparin (ULMWH), namely semuloparin (AVE5026) and compare it with routinely used unfractionated heparin (UF) and the low molecular weight heparins (LMWH), enoxaparin and bemiparin. In addition, RO-14, another ULMWH, was studied for comparison. Semuloparin is currently in clinical development for the prevention of venous thromboembolism. Semuloparin is prepared by a highly selective depolymerization of the heparin backbone by a phosphazene base which preserves the antithrombin (AT) binding sequence. The unique structural features of semuloparin differentiate it from LMWHs. Unlike other depolymerized heparins where theantithrombin (AT) affinity components and anti-Xa activity is decreased with the decrease in the molecular weight, semuloparin exhibits a relatively higher proportion of AT-binding components which translates into a higher anti-Xa activity.
In conclusion, this dissertation clearly demonstrates that different MW and affinity profiles of UF, LMW, and ULMW heparins contribute to the unique pharmacological effects of these agents. In addition, these studies illustrate that heparins enrichment with the high-affinity AT binding sequences, which results in a higher anti-FXa/FIIa ratio, promotes a better antithrombotic and safety profile compared to non-enriched heparin derivatives. Overall, this dissertation provides a comprehensive biochemical and pharmacological investigation in which not only the molecular weight dependence, but also the differences in structural composition of heparin and its derivatives were determined.
"],"dc:identifier":["https://ecommons.luc.edu/luc_diss/411"],"dc:subject":["antithrombotic","cancer","low molecular weight heparins","semuloparin","ultra low molecular weight heparins","unfractionated heparins","Pharmacology"],"dc:title":["Compositional Determinants of the Pharmacological Actions of Heparins"],"thesis:degree_discipline":["Educational Psychology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T02:55:31Z"}