Two syntheses of 2,4,6-trideoxy-4-methylthio-D-ribo-pyranose, a component of the oligosaccharide of esperamicins are described: an asymmetric synthesis starting from the propargylic alcohol dimer and the stereocontrolled transformation of D-fucose.

Aromatic azo compounds were efficiently cleaved by the horseradish peroxidase (HRP) into aromicdiazonium ions, during which an intense special absorption of the substrate disappeared completely. This furnished a sensitive spectrophotometric detection of 0.025–6.0 nm peroxidase. Kinetic characte...

The human immunodeficiency virus (HIV) epidemic is an important medical problem. Although combination drug regimens have produced dramatic decreases in viral load, current therapies do not provide a cure for HIV infection. We have used structure-based design and combinatorial medicinal chemistry...

A set of phosphonic acid derivatives (1–4) of pyridoxal 5′-phosphate (PLP) was synthesized and characterized biochemically using purified murine pyridoxal phosphatase (PDXP), also known as chronophin. The most promising compound 1 displayed primarily competitive PDXP inhibitory activity with a...

Pyridoxal kinase (PdxK, EC 2.7.1.35) is an important enzyme of vitamin B6 salvage pathway which is required for phosphorylation of B6 vitamers. In the present study, pyridoxal kinase (pdxK) gene from Leishmania donovani (LdPdxK) was cloned and a 33 kDa protein was expressed and kinetically chara...

The interaction between pyridoxal hydrochloride (HQ) and apoCopC was investigated using Fourier transform infrared spectroscopy (FTIR), isothermal titration calorimetry (ITC), circular dichroism (CD), fluorescence spectroscopy, three-dimensional (3D) fluorescence spectroscopy, fluorescence lifet...

Bovine serum albumin (BSA) catalyzes the o-rearrangement of the reactive electrophile, N-sulfooxy-2-acetylaminofluorene (NSF), a potential ultimate hepatocarcinogen in the rat, to the nonmutagenic sulfuric acid esters of 1- and 3-hydroxy-2-acetylaminofluorene. Conversion of NSF was proportional ...

The chemical synthesis of 3β,7β-dihydroxy-5-cholen-24-oic acid, triply conjugated by sulfuric acid at C-3, by N-acetylglucosamine (GlcNAc) at C-7, and by glycine or taurine at C-24, is described. These are unusual, major metabolites of bile acid found to be excreted in the urine of a patient w...

In Niemann-Pick disease, type C1, increased amounts of 3β,7β-dihydroxy-5-cholenoic acid are reported to be present in urinary bile acids. The compound occurs as a tri-conjugate, sulfated at C-3, N-acetylglucosamidated at C-7, and N-acylamidated with taurine or glycine at C-24. For sensitive LC...

Nucleophilic substitution of 5-bromotriazoloisoquinoline (3) and of 7-bromo-3-methyltriazolopyridine (6) proceeds readily to give a range of 5-substituted triazoloisoquinolines (4a)-(4e), and of 7-substituted triazolopyridines (7a)-(7h) respectively. Triazoloisoquinolines have been converted int...

An esperamicin core analog 4 with an epoxide trigger like that found in the related enediyne, dynemicin, was prepared. Surprisingly, it was found to be relatively stable; the p-aminophenyl substituent did not facilitate epoxide solvolysis to the extent that had been anticipated. A mild acid, pyr...

An enediyne analog (2, R=H) that is a hybrid of the core structures of esperamicin and dynemicin was prepared. The key step in its synthesis was a Reissert-type reaction that involved intramolecular addition of the anion of a Z-1,3-diyn-2-ene to an N-acyl tetrahydrophenathridinium intermediate. ...

Bicyclo[7.3.1]enediyne intermediates for the synthesis of analogs of BMY-46108 (5), a simple core analog of esperamicin, were prepared by two different routes. One involved fluoride-promoted cyclization of 1 followed by epoxide rearrangement. The other proceeded by a base-promoted cyclization of...

Background and Objectives: Voltage-sensitive calcium channel conductance is essential for the nervous system to signal a painful event. However, intrathecal administration of L-type calcium channel blockers does not provide analgesia. The present investigation was designed to assess the safety a...

Ziconotide is a selective peptide antagonist of the N-type calcium channel currently in clinical trials for analgesia. Ziconotide reached a maximal brain concentration of between 0.003 and 0.006% of the injected material per gram of tissue at 3–20 min after i.v. injection, and this decayed to b...

The purpose of the current study was to investigate the plausibility of delivery of ziconotide to the cerebrospinal fluid (CSF) via intranasal administration. Ziconotide was administered either in the form of solution or Kolliphor P 407 gels (KP 407) intranasally in Sprague–Dawley rats. The eff...

A synthetic procedure has been developed to enable the sequential regio-selective Suzuki-Miyaura cross-coupling of 1,4-dibromo-2-nitrobenzene with a variety of arylboronic acids. The first Suzuki coupling step, using a phosphine-free palladium catalyst at room temperature, gave selective couplin...

1.1. Blocking activities of α- and β-adrenoceptors by 4-(2-hydroxy-3-[(1-methyl-3-phenylpropyl)amino]propoxy)benzeneacetamide (KF4317) were tested on the isolated muscles, compared with the action of labetalol.2.2. In blocking the β1-adrenoceptor, KF4317 was almost as active as labetalol.3.3....

The examination of a key series of chromophore analogues of sandramycin (1) is detailed employing surface plasmon resonance to establish binding constants within a single high affinity bis-intercalation binding site 5′-d(GCATGC)2, and to establish the preference for sandramycin binding to 5′-d...

The preparation and examination of 2–22 constituting a systematic study of the chromophore of sandramycin (1) are detailed. Fluorescence quenching studies were used to establish binding constants for 1–24 within calf thymus DNA, within a single high affinity bis-intercalation binding site 5′-...