Controlling the self-assembly of cellulose nanocrystals (CNCs) requires precise control over their surface chemistry for the directed assembly of advanced nanocomposites with tailored mechanical, thermal, and optical properties. In this work, in contrast to traditional chemistries, we conducted highly selective click-chemistry functionalization of cellulose nanocrystals with complementary DNA strands via a three-step hybridization-guided process. By grafting terminally functionalized oligonucleotides through copper-free click chemistry, we successfully facilitated the assembly of brushlike DNA-modified CNCs into bundled nanostructures with distinct chiral optical dichroism in thin films.
View Article and Find Full Text PDFAm J Forensic Med Pathol
December 2024
Tolerance is the diminished response to a drug that occurs when that drug is repeatedly used, and the body adapts to its continued presence. This means that greater blood concentrations are required to achieve desired effects, produce impairment, or cause death. Without case-specific information, the pharmacodynamic impacts of a drug on an individual are difficult to ascertain based on its concentration alone.
View Article and Find Full Text PDFMitragynine is the primary active alkaloid in the leaves of the tropical tree Mitragyna speciosa, and goes by the popular names "Kratom", biak-biak and maeng da. Mitragynine is increasingly seen in forensic toxicology casework including driving under the influence of drugs and medicolegal death investigation cases. The toxicity of mitragynine continues to be debated in the scientific community as advocates highlight its long history of use in Southeast Asia and testimonials to its benefits by present-day users, while opponents point to an increasing number of adverse events tied to mitragynine use in Western societies.
View Article and Find Full Text PDFLoperamide (Imodium) has been accepted as a safe, effective, over-the-counter anti-diarrheal drug with low potential for abuse. It is a synthetic opioid that lacks central nervous system activity at prescribed doses, rendering it ineffective for abuse. Since 2012, however, the North Carolina Office of the Chief Medical Examiner has seen cases involving loperamide at supratherapeutic levels that indicate abuse.
View Article and Find Full Text PDFKappa-opioid agonists are particularly efficacious in the treatment of peripheral pain but suffer from central nervous system (CNS)-mediated effects that limit their development. One promising kappa-agonist is the peptidic compound CR665. Although not orally available, CR665 given i.
View Article and Find Full Text PDFThe neurotensin hexapapetide fragment NT(8-13) is a potent analgesic when administered directly to the central nervous system but does not cross the blood-brain barrier. A total of 43 novel derivatives of NT(8-13) were evaluated, with one, ABS212 (1), being most active in four rat models of pain when administered peripherally. Compound 1 binds to human neurotensin receptors 1 and 2 with IC(50) of 10.
View Article and Find Full Text PDFThe development of peptide beta-hairpins is problematic, because folding depends on the amino acid sequence and changes to the sequence can significantly decrease folding. Robust beta-hairpins that can tolerate such changes are attractive tools for studying interactions involving protein beta-sheets and developing inhibitors of these interactions. This paper introduces a new class of peptide models of protein beta-sheets that addresses the problem of separating folding from the sequence.
View Article and Find Full Text PDF[structure: see text] The widely used internal standard for NMR studies in aqueous solution DSS (sodium 4,4-dimethyl-4-silapentane-1-sulfonate) can interact with cationic peptides, diminishing its value for such studies. This paper introduces DSA (4,4-dimethyl-4-silapentane-1-ammonium trifluoroacetate) as a new internal standard that does not suffer from this problem.
View Article and Find Full Text PDFTwo quasi-aromatic compounds, namely, two dipyrrinone dyes (Xanthoglow and Kryptoglow), exhibited strong fluorescence. Therefore they were tested for laser action under flash-lamp pumping. These two dyes outperformed Coumarin 540A and exhibited a high degree of photostability when dissolved in 1,4-dioxane.
View Article and Find Full Text PDFRecent reports by Galeazzi and co-workers demonstrated the susceptibility of Abeta(1-42) to undergo dityrosine formation via peroxidase-catalyzed tyrosine cross-linking. We have formed dityrosine cross-links in Abeta(1-40) using these enzymatic conditions as well as a copper-H(2)O(2) method. The efficiency of dityrosine cross-link formation is strongly influenced by the aggregation state of Abeta; more dityrosine is formed when copper-H(2)O(2) or horseradish peroxidase-catalyzed oxidation is applied to fibrillar Abeta vs soluble Abeta.
View Article and Find Full Text PDFPrevious studies by Gellman and co-workers have elegantly shown that mirror-image beta-turns based upon d-Pro-Gly are especially good at stabilizing beta-hairpins and have demonstrated that peptide 1 [Arg-Trp-Gln-Tyr-Val-d-Pro-Gly-Lys-Phe-Thr-Val-Gln-NH2] folds into a well-defined beta-hairpin [Espinosa, J. F.; Gellman, S.
View Article and Find Full Text PDFThe biliary excretion of the sodium salts of 8-(2-ethanesulfonic acid)-3-ethyl-2,7,9-trimethyl-1,10-dihydro-11H-dipyrrin-1-one (xanthosulfonic acid) and a fluorescent analogue (8-desethyl-N,N'-carbonyl-kryptopyrromethenone-8-sulfonic acid) was compared in Mrp2-deficient (TR(-)) and normal rats. Both organic anions were excreted rapidly in bile in Mrp2-deficient rats, but the biliary excretion of the fluorescent sulfonate was impaired relative to normal controls. The rat clearly has efficient Mrp2-independent mechanisms for biliary efflux of these anions that are not used by bilirubin or its mono- and diglucuronides.
View Article and Find Full Text PDFA new, highly fluorescent (Phi(F) > or = 0.8) chromophore has been synthesized in one step from dipyrrinones by reaction with N,N-carbonyldiimidazole to form the 3H,5H-dipyrrolo[1,2-c:2',1'-f]pyrimidine-3,5-dione nucleus.
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