Heparin Derivatives as Inhibitors of BACE-1, the Alzheimer's -Secretase, with Reduced Activity against Factor Xa and
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- 作者：Susannah J. Patey ; Elizabeth A. Edwards ; Edwin A. Yates ; Jeremy E. Turnbull
- 刊名：Journal of Medicinal Chemistry
- 出版年：2006
- 出版时间：October 5, 2006
- 年：2006
- 卷：49
- 期：20
- 页码：6129 - 6132
- 全文大小：48K
- 年卷期：v.49,no.20(October 5, 2006)
- ISSN：1520-4804
文摘
Heparan sulfate (HS) regulates processing of the amyloid precursor protein by the Alzheimer's 
chars/beta2.gif" BORDER=0 ALIGN="middle">-secretase(BACE-1). An HS analogue, porcine intestinal mucosal heparin, was systematically modified at the principalpositions of O-sulfation and N-sulfation/acetylation and tested for BACE-1 inhibitory and anti factor Xaactivities. The derivative with the highest anti-BACE-1 to anti-Xa activity ratio contained N-acetyl and2-O- and 6-O-sulfates and also exhibited attenuated activities against cathepsin-D and renin, two otherstructurally related aspartyl proteases.
chars/beta2.gif" BORDER=0 ALIGN="middle">-secretase(BACE-1). An HS analogue, porcine intestinal mucosal heparin, was systematically modified at the principalpositions of O-sulfation and N-sulfation/acetylation and tested for BACE-1 inhibitory and anti factor Xaactivities. The derivative with the highest anti-BACE-1 to anti-Xa activity ratio contained N-acetyl and2-O- and 6-O-sulfates and also exhibited attenuated activities against cathepsin-D and renin, two otherstructurally related aspartyl proteases.