Enzymatic Generation of Highly Anticoagulant Bovine Intestinal Heparin

Li Fu; Kevin Li; Daisuke Mori; Makoto Hirakane; Lei Lin; Navdeep Grover; Payel Datta; Yanlei Yu; Jing Zhao; Fuming Zhang; Murat Yalcin; Shaker A. Mousa; Jonathan S. Dordick; Robert J. Linhardt

doi:10.1021/acs.jmedchem.7b01269

Enzymatic Generation of Highly Anticoagulant Bovine Intestinal Heparin

Li Fu, Kevin Li, Daisuke Mori, Makoto Hirakane, Lei Lin, Navdeep Grover, Payel Datta, Yanlei Yu, Jing Zhao, Fuming Zhang, Murat Yalcin, Shaker A. Mousa, Jonathan S. Dordick, Robert J. Linhardt

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

Unlike USP porcine heparin, bovine intestinal heparin (BIH) has a low anticoagulant activity. Treatment with 6-OST-1, -3, and/or 3-OST-1 afforded two remodeled heparins that met USP heparin activity and Mw specifications. We explored the pharmacodynamics and pharmacokinetics in a rabbit model. We conclude that a modest increase in the content of 3-O-sulfo groups in BIH increases the number of antithrombin III binding sites, making remodeled BIH behave similarly to pharmaceutical heparin.

Original language	English
Pages (from-to)	8673-8679
Number of pages	7
Journal	Journal of Medicinal Chemistry
Volume	60
Issue number	20
DOIs	https://doi.org/10.1021/acs.jmedchem.7b01269
State	Published - 26 Oct 2017
Externally published	Yes

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title = "Enzymatic Generation of Highly Anticoagulant Bovine Intestinal Heparin",

abstract = "Unlike USP porcine heparin, bovine intestinal heparin (BIH) has a low anticoagulant activity. Treatment with 6-OST-1, -3, and/or 3-OST-1 afforded two remodeled heparins that met USP heparin activity and Mw specifications. We explored the pharmacodynamics and pharmacokinetics in a rabbit model. We conclude that a modest increase in the content of 3-O-sulfo groups in BIH increases the number of antithrombin III binding sites, making remodeled BIH behave similarly to pharmaceutical heparin.",

author = "Li Fu and Kevin Li and Daisuke Mori and Makoto Hirakane and Lei Lin and Navdeep Grover and Payel Datta and Yanlei Yu and Jing Zhao and Fuming Zhang and Murat Yalcin and Mousa, {Shaker A.} and Dordick, {Jonathan S.} and Linhardt, {Robert J.}",

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doi = "10.1021/acs.jmedchem.7b01269",

language = "English",

volume = "60",

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TY - JOUR

T1 - Enzymatic Generation of Highly Anticoagulant Bovine Intestinal Heparin

AU - Fu, Li

AU - Li, Kevin

AU - Mori, Daisuke

AU - Hirakane, Makoto

AU - Lin, Lei

AU - Grover, Navdeep

AU - Datta, Payel

AU - Yu, Yanlei

AU - Zhao, Jing

AU - Zhang, Fuming

AU - Yalcin, Murat

AU - Mousa, Shaker A.

AU - Dordick, Jonathan S.

AU - Linhardt, Robert J.

PY - 2017/10/26

Y1 - 2017/10/26

N2 - Unlike USP porcine heparin, bovine intestinal heparin (BIH) has a low anticoagulant activity. Treatment with 6-OST-1, -3, and/or 3-OST-1 afforded two remodeled heparins that met USP heparin activity and Mw specifications. We explored the pharmacodynamics and pharmacokinetics in a rabbit model. We conclude that a modest increase in the content of 3-O-sulfo groups in BIH increases the number of antithrombin III binding sites, making remodeled BIH behave similarly to pharmaceutical heparin.

AB - Unlike USP porcine heparin, bovine intestinal heparin (BIH) has a low anticoagulant activity. Treatment with 6-OST-1, -3, and/or 3-OST-1 afforded two remodeled heparins that met USP heparin activity and Mw specifications. We explored the pharmacodynamics and pharmacokinetics in a rabbit model. We conclude that a modest increase in the content of 3-O-sulfo groups in BIH increases the number of antithrombin III binding sites, making remodeled BIH behave similarly to pharmaceutical heparin.

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U2 - 10.1021/acs.jmedchem.7b01269

DO - 10.1021/acs.jmedchem.7b01269

M3 - Article

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AN - SCOPUS:85032449266

SN - 0022-2623

VL - 60

SP - 8673

EP - 8679

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 20

ER -

Enzymatic Generation of Highly Anticoagulant Bovine Intestinal Heparin

Abstract

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