Dataset Information

Chemical and Physical Variability in Structural Isomers of an l/d ?-Sheet Peptide Designed To Inhibit Amyloidogenesis.

ABSTRACT: There has been much interest in synthetic peptides as inhibitors of aggregation associated with amyloid diseases. Of particular interest are compounds that target the cytotoxic soluble oligomers preceding the formation of mature, nontoxic fibrils. This study explores physical and chemical differences between two de novo-designed peptides that share an identical primary structure but differ in backbone chirality at six key positions. We show that the presence of alternating l/d-amino acid motifs dramatically increases aqueous solubility, enforces ?-sheet secondary structure, and inhibits aggregation of the ?-amyloid peptide implicated in Alzheimer's disease, in addition to neutralizing its cytotoxicity. In contrast, the all-l-amino acid isomer does not form ?-sheet structure and is insoluble and inactive.

SUBMITTER: Maris NL

PROVIDER: S-EPMC5801053 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Chemical and Physical Variability in Structural Isomers of an l/d α-Sheet Peptide Designed To Inhibit Amyloidogenesis.

Maris Nathan L NL Shea Dylan D Bleem Alissa A Bryers James D JD Daggett Valerie V

Biochemistry 20171219 5

There has been much interest in synthetic peptides as inhibitors of aggregation associated with amyloid diseases. Of particular interest are compounds that target the cytotoxic soluble oligomers preceding the formation of mature, nontoxic fibrils. This study explores physical and chemical differences between two de novo-designed peptides that share an identical primary structure but differ in backbone chirality at six key positions. We show that the presence of alternating l/d-amino acid motifs ...[more]

PMID: 29202245

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Project description:Nicotine salt-based e-liquids deliver nicotine more rapidly and efficiently to electronic nicotine delivery system (ENDS) users than freebase nicotine formulations. Nicotine salt-based products represent a substantial majority of the United States ENDS market. Despite the popularity of nicotine salt formulations, the chemical and physical characteristics of aerosols produced by nicotine salt e-liquids are still not well understood. To address this, this study reports the harmful and potentially harmful constituents (HPHCs) and particle sizes of aerosols produced by laboratory-made freebase nicotine and nicotine salt e-liquids. The nicotine salt e-liquids were formulated with benzoic acid, citric acid, lactic acid, malic acid, or oxalic acid. The nicotine salt aerosols had different HPHC profiles than the freebase nicotine aerosols, indicating that the carboxylic acids were not innocent bystanders. The polycarboxylic acid e-liquids containing citric acid, malic acid, or oxalic acid produced higher acrolein yields than the monocarboxylic acid e-liquids containing benzoic acid or lactic acid. Across most PG:VG ratios, nicotine benzoate or nicotine lactate aerosols contained the highest nicotine quantities (in %) and the highest nicotine yields (per milligram of aerosol). Additionally, the nicotine benzoate and nicotine lactate e-liquids produced the highest carboxylic acid yields under all tested conditions. The lower acid yields of the citric, malic, and oxalic acid formulations are potentially due to a combination of factors such as lower transfer efficiencies, lower thermostabilities, and greater susceptibility to side reactions because of their additional carboxyl groups serving as new sites for reactivity. For all nicotine formulations, the particle size characteristics were primarily controlled by the e-liquid solvent ratios, and there were no clear trends between nicotine salt and freebase nicotine aerosols that indicated nicotine protonation affected particle size. The carboxylic acids impacted aerosol output, nicotine delivery, and HPHC yields in distinct ways such that interchanging them in ENDS can potentially cause downstream effects.

Dataset Information

Chemical and Physical Variability in Structural Isomers of an l/d ?-Sheet Peptide Designed To Inhibit Amyloidogenesis.

Publications

Chemical and Physical Variability in Structural Isomers of an l/d α-Sheet Peptide Designed To Inhibit Amyloidogenesis.

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