Formation Kinetics of Insulin-Based Amyloid Gels and the Effect of Added Metalloporphyrins

Pasternack, Robert F.; Gibbs, Esther J.; Sibley, Scott P.; Lauren, Woodard; Hutchinson, Peter H.; Genereux, Joseph C.; Kristian, Kathleen E.

doi:10.1529/biophysj.105.068650

Cited by 28 publications

(35 citation statements)

References 48 publications

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“…It was previously shown that anionic tetrakis(4‐sulfonatophenyl)porphine inhibits insulin fibrillization, while cationic tetrakis( N ‐methylpyridinium‐4‐yl)porphine has no significant effect on amyloids formation . Here, we observed the same effect for metal‐free tetraphenylporphyrins—inhibitory effect on insulin aggregation of amino‐substituted (cation‐forming) TPPN4 was essentially lower than that for carboxy‐substituted (anion‐forming) TNNC4.…”

Section: Resultssupporting

confidence: 78%

“…Besides, the ability of porphyrin and hematin to inhibit tau fibril assembly was shown as well . The series of cationic tetrakis( N ‐methylpyridinium‐4‐yl)porphine and anionic tetrakis(4‐sulfonatophenyl)porphine complexes having a range of central metal atoms were studied for their effect on insulin aggregation; high inhibitory activity of anionic metalloporphyrins and their effect on structure of insulin aggregates were reported …”

Section: Introductionmentioning

confidence: 99%

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Study of tetraphenylporphyrins as modifiers of insulin amyloid aggregation

Chernii

Losytskyy

Kelm

et al. 2019

J of Molecular Recognition

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Amyloid fibrils are rigid β-pleated protein aggregates that are connected with series of harmful diseases and at the same time are promising as base for novel nanomaterials. Thus, design of compounds able to inhibit or redirect those aggregates formation is important both for the biomedical aims and for nanotechnology applications. Here, we studied the effect of tetraphenylporphyrins (metal free, their Cu and Pd complexes, and those functionalized by carboxy and amino groups on periphery) on insulin amyloid self-assembling. The strongest impact on insulin aggregation was demonstrated by a metal-free porphyrin bearing four carboxy groups. This compound strongly suppresses insulin aggregation (about 88% reduction in amyloid-sensitive probe emission) inducing formation of fibrils with the length close to this of free insulin (1.7 ± 0.6 μm as compared with 1.4 ± 0.4 μm, respectively) with an essentially reduced tendency to lateral aggregation. Contrarily, the presence of tetraphenylporphyrin containing four amino groups only slightly affects fibrils' morphology and makes weaker impact on insulin aggregation yield (about 44% reduction). This is explained by the ability of aromatic carboxy groups of 5,10,15,20-(tetra-4carboxyphenyl)porphyrin to interact with complementary protein-binding groups and thus stabilize the supramolecular complex. For 5,10,15,20-(tetra-4aminophenyl)porphyrin, full protonation takes place in acidic medium of protein aggregation reaction; this results in the high positive charge of TPPN4 (equal or close to +6) and hence higher contribution of coulombic repulsion to interaction of TPPN4 with insulin. One more possible mechanism of the lower inhibition effect of TPPN4 as compared with TPPC4 could be the more restricted possibility of the former as compared with the latter to form H bonds with insulin groups. It was also shown that metal-free, Pd-containing, and Cu-containing tetraphenylporphyrins without peripheral substituents make almost the same impact on the protein self-assembling. We suppose this to be due to coordination saturation of these metal atoms.

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Section: Resultssupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Study of tetraphenylporphyrins as modifiers of insulin amyloid aggregation

Chernii

Losytskyy

Kelm

et al. 2019

J of Molecular Recognition

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“…For instance, H 2 PcS 4 suppresses the formation of ␣-synuclein amyloid, a pathological factor in Parkinson's disease (13). Tetrasulfonated porphyrins inhibit the aggregation of insulin (16), and hemin analogs delay fibril formation by the A/␤ peptide associated with Alzheimer's disease (7). These observations raise the possibility that cyclic tetrapyrroles have similar mechanisms of action in slowing the formation of a variety of pathological protein aggregates.…”

mentioning

confidence: 99%

Cyclic Tetrapyrrole Sulfonation, Metals, and Oligomerization in Antiprion Activity

Caughey¹,

Priola²,

Kocisko³

et al. 2007

Antimicrob Agents Chemother

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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.

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“…For example, the influence of added metalloporphyrins on the rate and extent of gel formation of insulin was shown in Ref. [20]. Enhancement of fluorescence of poly(phenylene ethylene) substituted with anionic 3-sulfonatopropyloxy groups (PPESO 3 ) by bovine serum albumin was reported in [21], while fluorescence quenching of PPESO 3 by three cationic oxacarbocyanine dyes was demonstrated in [22] where the quenching efficiency was shown to be controlled by the stability of the polymer-dye association complex.…”

Section: Introductionmentioning

confidence: 99%