Heparan sulfate (HS) regulates processing of the amyloid precursor protein by the Alzheimer's
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-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.