Copper-Catalyzed Covalent Dimerization of Near-Infrared Fluorescent Cyanine Dyes: Synergistic Enhancement of Photoacoustic Signals for Molecular Imaging of Tumors.

Photoacoustic (PA) imaging relies on the absorption of light by chromophores to generate acoustic waves used to delineate tissue structures and physiology. Here, we demonstrate that Cu(II) efficiently catalyzes the dimerization of diverse near-infrared (NIR) cyanine molecules, including a peptide conjugate. NMR spectroscopy revealed a C-C covalent bond along the heptamethine chains, creating stable molecules under conditions such as a wide range of solvents and pH mediums.

Universal Subsidized Continuous Glucose Monitoring Funding for Young People With Type 1 Diabetes: Uptake and Outcomes Over 2 Years, a Population-Based Study.

Objective: Continuous glucose monitoring (CGM) is increasingly used in type 1 diabetes management; however, funding models vary. This study determined the uptake rate and glycemic outcomes following a change in national health policy to introduce universal subsidized CGM funding for people with type 1 diabetes aged <21 years.

Research Design And Methods: Longitudinal data from 12 months before the subsidy until 24 months after were analyzed.

Quantifying dynamic range in red blood cell energetics: Evidence of progressive energy failure during storage.

Background: During storage, red blood cells (RBCs) undergo significant biochemical and morphologic changes, referred to collectively as the "storage lesion". It was hypothesized that these defects may arise from disrupted oxygen-based regulation of RBC energy metabolism, with resultant depowering of intrinsic antioxidant systems.

Study Design And Methods: As a function of storage duration, the dynamic range in RBC metabolic response to three models of biochemical oxidant stress (methylene blue, hypoxanthine/xanthine oxidase, and diamide) was assessed, comparing glycolytic flux by NMR and UHPLC-MS methodologies.

Bedside colonoscopy in intensive care units: indications, techniques, and outcomes.

Background: Colonoscopy performed in critically ill patients is poorly documented in the literature. The clinical setting is completely different from routine outpatient colonoscopy with different aims and techniques. We proposed to examine the role of urgent colonoscopy in critically ill patients.

Rapid screening and structural elucidation of a novel sibutramine analogue in a weight loss supplement: 11-desisobutyl-11-benzylsibutramine.

A novel analogue of sibutramine, 11-desisobutyl-11-benzylsibutramine, has been discovered. During routine ion mobility spectrometry (IMS) screening of a weight loss supplement collected at an US FDA import operation facility an unknown peak was observed. Further analysis of the supplement by liquid chromatography-mass spectrometry (LC-MS) and high resolution mass spectrometry revealed an unknown peak with a relative retention time of 1.

A new nucleoside analogue with potent activity against mutant sr39 herpes simplex virus-1 (HSV-1) thymidine kinase (TK).

Nucleoside analogues, such as penciclovir, ganciclovir, acyclovir, and their fluoro-substituted derivatives, have wide utility as antivirals. Among these analogues, FHBG ((18)F-Fluorohydroxybutylguanine) is a well-validated PET (positron emission tomography) probe for monitoring reporter gene expression. To evaluate whether or not imposing rigidity into the flexible side chain of FHBG 4 could also impact its interaction, with amino acid residues within the binding site of HSV1-TK (Herpes Simplex Virus-1 Thymidine Kinase), thus influencing its cytotoxic activity.

Understanding Dichromic Fluorescence Manifested in Certain ICG Analogs.

Fluorescence has advanced our understanding in various aspects of biological processes. Fluorescence in the near infrared (NIR) region avoids background autofluorescence from biological samples leading to improved image quality. In searching for indocyanine green (ICG) analogs that can be attached to biomolecules, we observed that dichromic fluorescence manifested in some mono reactive-group functionalized ICG analogs.

A second look at mini-protein stability: analysis of FSD-1 using circular dichroism, differential scanning calorimetry, and simulations.

Mini-proteins that contain <50 amino acids often serve as model systems for studying protein folding because their small size makes long timescale simulations possible. However, not all mini-proteins are created equal. The stability and structure of FSD-1, a 28-residue mini-protein that adopted the betabetaalpha zinc-finger motif independent of zinc binding, was investigated using circular dichroism, differential scanning calorimetry, and replica-exchange molecular dynamics.

Spectroscopic identification of tri-n-octylphosphine oxide (TOPO) impurities and elucidation of their roles in cadmium selenide quantum-wire growth.

Tri-n-octylphosphine oxide (TOPO) is the most commonly used solvent for the synthesis of colloidal nanocrystals. Here we show that the use of different batches of commercially obtained TOPO solvent introduces significant variability into the outcomes of CdSe quantum-wire syntheses. This irreproducibility is attributed to varying amounts of phosphorus-containing impurities in the different TOPO batches.

pH-dependent optical properties of synthetic fluorescent imidazoles.

An imidazole moiety is often found as an integral part of fluorophores in a variety of fluorescent proteins and many such proteins display pH-dependent light emission. In contrast, synthetic fluorescent compounds with incorporated imidazoles are rare and have not been studied as pH probes. In this report, the richness of imidazole optical properties, including pH sensitivity, was demonstrated by means of a novel imidazole-based fluorophore 1H-imidazol-5-yl-vinylbenz[e]indolium.

Near-infrared fluorescent pH-sensitive probes via unexpected barbituric acid mediated synthesis.

Novel near-infrared pyrimidine-fused pH fluorescent probes were prepared by an unusual barbiturate-mediated debenzoindolation and subsequent heteroannulation. A plausible mechanistic pathway is proposed, and the final structures were further elucidated by 2D-NMR. All new compounds are highly fluorescent in the near-infrared region and possess excellent spectral sensitivities to environmental pH changes.

c[D-pro-Pro-D-pro-N-methyl-Ala] adopts a rigid conformation that serves as a scaffold to mimic reverse-turns.

Naturally occurring cyclic tetrapeptides (CTPs) such as tentoxin (Halloin et al., Plant Physiol 1970, 45, 310-314; Saad, Phytopathology 1970, 60, 415-418), ampicidin (Darkin-Rattray, Proc Natl Acad Sci USA 1996, 93, 13143-13147), HC-toxin (Walton, Proc Natl Acad Sci USA 1987, 84, 8444-8447), and trapoxin (Yoshida and Sugita, Jpn J Cancer Res 1992, 83, 324-328; Itazaki et al., J Antibiot (Tokyo) 1990, 43, 1524-1532) have a wide range of biological activity and potential use ranging from herbicides (Walton, Proc Natl Acad Sci USA 1987, 84, 8444-8447; Judson, J Agric Food Chem 1987, 35, 451-456) to therapeutics (Loiseau, Biopolymers 2003, 69, 363-385) for malaria (Darkin-Rattray, Proc Natl Acad Sci USA 1996, 93, 13143-13147) and cancer (Yoshida and Sugita, Jpn J Cancer Res 1992, 83, 324-328).

Design, synthesis, and metal binding of novel Pseudo- oligopeptides containing two phosphinic acid groups.

Phosphinic compounds have potential as amide-bond mimetics in the development of novel peptidomimetics, enzyme inhibitors, and metal-binding ligands. Novel pseudo-oligopeptides with two phosphinic acid groups embedded in the peptide backbone serving as amide-bond surrogates, Psi[P(O,OH)--CH(2)], were targeted. A series of linear and cyclic pseudo-oligopeptides with two phosphinic acid groups arrayed at different positions in the peptide sequence were designed, including Ac--Phe--{(R,S)--AlaPsi[P(O,OH)--CH(2)]Gly}(2)--NH(2) (P2), Ac--NH--(R,S)--AlaPsi[P(O,OH)--CH(2)]Gly--Phe--(R,S)--AlaPsi[P(O,OH)--CH(2)]Gly--NH(2) (P3), Ac--NH--(R,S)--AlaPsi[P(O,OH)--CH(2)]Gly--Phe--Phe--(R,S) --AlaPsi[P(O,OH)--CH(2)]Gly--NH(2) (P4), cyclo{NH--(R,S)--AlaPsi[P(O,OH)--CH(2)]Gly--Phe}(2) (P5), and cyclo[NH--(R,S)--AlaPsi[P(O,OH)--CH(2)]Gly--Phe--Phe](2) (P6).

Determination of 77Se-77Se and 77Se-13C J-coupling parameters for the clusters [Re5OsSe8(CN)6]3- and [Re4Os2Se8(CN)6]2-.

We have investigated rarely observed 77Se J-couplings (spin-spin couplings) in the mixed-metal face-capped octahedral clusters [Re5OsSe8(CN)6]3- and [Re4Os2Se8(CN)6]2- at natural abundance. To the best of our knowledge, these are the first observations of Se-Se spin-spin interactions between mu3-Se sites, important for stereochemical assignments in hexarhenium analogues, Chevrel phase materials, and similar cluster materials. NMR techniques such as COSY, INADEQUATE, and 2D J-resolved spectroscopy have been used in conjunction to study these interactions.

Novel carbonyl and nitrile products from reactive chlorinating species attack of lysosphingolipid.

Lysosphingolipids are important lipid signaling molecules that are associated predominantly with high density lipoproteins (HDL) in human plasma. Further, HDL has been shown to be a target for the reactive chlorinating species (RCS) produced by myeloperoxidase (MPO). Accordingly, RCS attack of lysosphingolipids was characterized in these studies.

Novel trihydroxamate-containing peptides: design, synthesis, and metal coordination.

Novel trihydroxamate-containing peptides were designed to mimic desferrioxamine (Desferal(R), DFO, a naturally occurring siderophore) but possess distinct conformational restrictions and varied lipophilicity to probe structure vs. metal coordination. The synthesis was performed via fragment condensation of hydroxamate-containing oligopeptides such as Fmoc-Leu- Psi[CON(OBz)]-Phe-Ala-Pro-OH and H-Leu-Psi[CON(OBz)]-Phe-Ala-Pro-OBu(t) (Fmoc: 9-fluor enylmethoxycarbonyl; OBz: benzyl; OBu(t): tert-butyl) either in solution or on a solid support.

Synthesis and characterization of a [3-15N]-labeled cis-syn thymine dimer-containing DNA duplex.

Cis-syn thymine dimers are the major photoproducts of DNA and are the principal cause of mutations induced by sunlight. To better understand the nature of base pairing with cis-syn thymine dimers, we have synthesized a decamer oligodeoxynucleotide (ODN) containing a cis-syn thymine dimer labeled at the N3 of both T's with 15N by two efficient routes from [3-15N]-thymidine phosphoramidite. In the postsynthetic irradiation route, an ODN containing an adjacent pair of [3-15N]-labeled T's was irradiated and the cis-syn dimer-containing ODN isolated by HPLC.

Myeloperoxidase-derived 2-chlorohexadecanal forms Schiff bases with primary amines of ethanolamine glycerophospholipids and lysine.

Numerous studies have suggested relationships between myeloperoxidase, inflammation, and atherosclerosis. MPO-derived reactive chlorinating species (RCS) attack membrane plasmalogens releasing alpha-chloro-fatty aldehydes (alpha-Cl-FALDs) including 2-chlorohexadecanal (2-ClHDA). The molecular targets of alpha-Cl-FALDs are not known.

Synthesis of an unusual branched-chain sugar, 5-C-methyl-L-idopyranose for SAR studies of pyranmycins: implication for the future design of aminoglycoside antibiotics.

The syntheses of a challenging branched-chain sugar and several L-sugars have been accomplished. Their application in studies of the antibacterial activity of pyranmycins is reported, which could provide new strategies for the future design of aminoglycoside antibiotics.

Oxidative cross-linking of tryptophan to glycine restrains matrix metalloproteinase activity: specific structural motifs control protein oxidation.

Matrix metalloproteinases (MMPs) function in homeostatic and repair processes, but unregulated catalysis by these extracellular proteinases leads to the pathological destruction of tissue proteins. An important mechanism for controlling enzyme activity might involve hypochlorous acid (HOCl), a potent oxidant produced by the myeloperoxidase system of phagocytes. We have shown that inactivation of MMP-7 (matrilysin) by HOCl coincides with the formation of a novel oxidation product, WG-4, through modification of adjacent tryptophan and glycine residues and loss of 4 atomic mass units.

Lysine residues direct the chlorination of tyrosines in YXXK motifs of apolipoprotein A-I when hypochlorous acid oxidizes high density lipoprotein.

Oxidized lipoproteins may play an important role in the pathogenesis of atherosclerosis. Elevated levels of 3-chlorotyrosine, a specific end product of the reaction between hypochlorous acid (HOCl) and tyrosine residues of proteins, have been detected in atherosclerotic tissue. Thus, HOCl generated by the phagocyte enzyme myeloperoxidase represents one pathway for protein oxidation in humans.

Consequences of single-site mutations in the intestinal fatty acid binding protein.

The intestinal fatty acid binding protein (IFABP) is a small (15 kDa) protein consisting mostly of 10 antiparallel beta-strands (A-J) and a small helical region that serves as a portal for the ligand. Two beta-sheet structures (strands A-E and F-J) surround a cavity into which the ligand binds. In this work, we investigated how changes in the side chains of specific residues are propagated through the structure.