NMR spectroscopy and surface tension measurements applied to the study of self-association of casopitant mesylate, a novel NK1 antagonist

Provera, Stefano; Cimarosti, Zadeo; Turco, Lucilla; Casazza, Andrea; Caivano, Grazia; Marchioro, Carla

doi:10.1016/j.jpba.2010.08.006

Cited by 1 publication

(2 citation statements)

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Section: Methodsmentioning

confidence: 99%

“…The tubes were preincubated in a 37 °C water bath for 1 h. Sample tubes were removed from the bath and placed in a temperature-controlled environment while the surface tension was measured using a Du Nouÿ ring. CMCs were generated using segmented linear regression fitting methods with GraphPad Prism v5.0, as described by Provera et al 28 Dynamic light scattering (DLS) was utilized to investigate the size distribution of the detergents under experiment conditions. Each detergent was prepared in 1 M acetate buffer at the optimal concentration of detergent (described above).…”

Section: ■ Introductionmentioning

confidence: 99%

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Detergent-Mediated Formation of β-Hematin: Heme Crystallization Promoted by Detergents Implicates Nanostructure Formation for Use as a Biological Mimic

Sandlin

Fong

Stiebler

et al. 2016

Crystal Growth & Design

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Hemozoin is a unique biomineral that results from the sequestration of toxic free heme liberated as a consequence of hemoglobin degradation in the malaria parasite. Synthetic neutral lipid droplets (SNLDs) and phospholipids were previously shown to support the rapid formation of β-hematin, abiological hemozoin, under physiologically relevant pH and temperature, though the mechanism by which heme crystallization occurs remains unclear. Detergents are particularly interesting as a template because they are amphiphilic molecules that spontaneously organize into nanostructures and have been previously shown to mediate β-hematin formation. Here, 11 detergents were investigated to elucidate the physicochemical properties that best recapitulate crystal formation in the parasite. A strong correlation between the detergent’s molecular structure and the corresponding kinetics of β-hematin formation was observed, where higher molecular weight polar chains promoted faster reactions. The larger hydrophilic chains correlated to the detergent’s ability to rapidly sequester heme into the lipophilic core, allowing for crystal nucleation to occur. The data presented here suggest that detergent nanostructures promote β-hematin formation in a similar manner to SNLDs and phospholipids. Through understanding mediator properties that promote optimal crystal formation, we are able to establish an in vitro assay to probe this drug target pathway.

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Section: Methodsmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%