Cyclic tetrapyrrole sulfonation, metals, and oligomerization in antiprion activity.

Abstract:

:Cyclic tetrapyrroles are among the most potent compounds with activity against transmissible spongiform encephalopathies (TSEs; or prion diseases). Here the effects of differential sulfonation and metal binding to cyclic tetrapyrroles were investigated. Their potencies in inhibiting disease-associated protease-resistant prion protein were compared in several types of TSE-infected cell cultures. In addition, prophylactic antiscrapie activities were determined in scrapie-infected mice. The activity of phthalocyanine was relatively insensitive to the number of peripheral sulfonate groups but varied with the type of metal bound at the center of the molecule. The tendency of the various phthalocyanine sulfonates to oligomerize (i.e., stack) correlated with anti-TSE activity. Notably, aluminum(III) phthalocyanine tetrasulfonate was both the poorest anti-TSE compound and the least prone to oligomerization in aqueous media. Similar comparisons of iron- and manganese-bound porphyrin sulfonates confirmed that stacking ability correlates with anti-TSE activity among cyclic tetrapyrroles.

authors

Caughey WS,Priola SA,Kocisko DA,Raymond LD,Ward A,Caughey B

doi

10.1128/AAC.01599-06

subject

Has Abstract

pub_date

2007-11-01 00:00:00

pages

3887-94

issue

11

eissn

0066-4804

issn

1098-6596

pii

AAC.01599-06

journal_volume

51

pub_type

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