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: Winslow S Caughey, Suzette A Priola, David A Kocisko, Lynne D Raymond, Anne Ward, Byron Caughey
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 51 Issue 11 Pg. 3887-94 (Nov 2007) ISSN: 0066-4804 [Print] United States
• PMID: 17709470 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Indoles
• Isoindoles
• Metals
• PrPSc Proteins
• Sulfonic Acids
• Tetrapyrroles
• phthalocyanine

Topics

• Animals
• Blotting, Western
• Cells, Cultured
• Cricetinae
• Dimerization
• Gene Expression (drug effects)
• Indoles (chemistry, pharmacology)
• Isoindoles
• Metals (chemistry, metabolism)
• Mice
• Mice, Transgenic
• Molecular Structure
• PrPSc Proteins (genetics, metabolism)
• Prion Diseases (genetics, metabolism, prevention & control)
• Sulfonic Acids (chemistry, metabolism)
• Tetrapyrroles (chemistry, metabolism, pharmacology)