Wendell Wierenga

Characteristics of N-formyl-methionyl-leucyl-phenylalanine as an inducer of lysosomal enzyme release from human neutrophils.

N-Formyl-methionyl-leucyl-phenylalanine (FMLP) stimulated a timeand concentration-dependent release of granule associatedβ-glucuronidase and lysozyme but not cytoplasmic lactate dehydrogenase from human neutrophils. Maximum discharge of lysosomal enzymes occurred two minutes after cell contact with FMLP. The percent of total enzyme activity released is insignificant when cells are not preincubated with cytochalasin B prior to being exposed to FMLP (10−10-10−7 M); although 11.2 ± 1.3 and 12.4 ±1.1% of total activity forβ-glucuronidase and lysozyme, respectively, is secreted from neutrophils with 10−4 M FMLP in the absence of cytochalasin B. FMLP-stimulated release of lysosomal enzymes occurs but is significantly curtailed in the absence of extracellular calcium. Incubation of neutrophils with EGTA in calcium-free medium, however, had no effect on FMLP-elicited lysosomal enzyme extrusion. 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8), a purported antagonist of intracellular calcium, demonstrated a dose-dependent inhibition of FMLP-induced release ofβ-glucuronidase and lysozyme from cytochalasin B-treated neutrophils in the absence of extracellular calcium. This effect of TMB-8 could be reversed with the addition of calcium to the extracellular medium. These studies indicate that TMB-8 may be useful in elucidating the role of calcium in the mechanism of lysosomal enzyme release.

Stereochemical control as a function of protecting-group participation in 2-deoxy-D-erythro-pentofuranosyl nucleosides☆

Abstract Possible features controlling the anomeric ratios in the synthesis of the antiviral antibiotic dihydro-5-azathymidine have been examined. Replacement of the 3- and 5-(4-methylbenzoyl) protecting groups in 2-deoxy- D - erythro -pentofuranosyl chloride by benzyl groups led to changes in anomeric ratios in stannic chloride-mediated condensations with both 5-methyl-2,4-bis(trimethylsilyl)triazine and 2,4-bis(trimethylsilyl)thymine. Analysis of the results suggested that steric elements, and more importantly, participating factors, of both the 3- and 5-protecting groups affect the anomeric ratios.

A versatile and efficient process to 3-substituted indoles from anilines

Abstract Borane-mediated reductive elimination of α-thiomethyl-, α-hydroxy, or α-alkoxy-, α′-substituted oxindoles affords 3-substituted indoles in high yield. Isatins, available via several routes from oxindoles, also afford indoles.

Chapter 16 Interferon Inducers

Publisher Summary Various studies show interferons are glycoproteins found in many cell types, whose production is induced by a chemically diverse group of agents and whose activities include antiviral, anticancer, and immunomodulatory. Clinically, exogenous interferon has been examined as a prophylactic anti-viral agent against such localized infections as vaccinia, rhinovirus, and influenza and therapeutically against vaccinia, herpetic keratitis, and genital herpes. Systemic viral infections including varicella-zoster, cytomegalovirus, and chronic hepatitis-B have also been challenged with interferon. Interferon therapy has been administered to patients with acute leukemia, recurrent breast cancer, multiple myeloma, juvenile larynx papilloma, and osteosarcoma. This chapter discusses the area of interferon inducers with particular emphasis on low molecular weight inducers. On the induction process, the chapter goes into how uptake of virus by a host cell begins the viral infection process of uncoating the protein coat of the invading virus, the viralnucleic acid reproduced, how this acid stimulates the messenger RNA (mRNA) of the host cell for translation into interferons and the protection process initiated by the secretions. A table lists the classification of interferons into TYPE I (Antiviral) and TYPE II (Immune) [γ]. Regarding the substances those induce interferon, one phenomenon is common to all inducers and that is hypo-reactivity, involving the loss of an interferon response on the part of the host upon sequential administration of an inducer-its onset and degree is inducer dependent. The inducers considered are high molecular weight inducers and low molecular weight interferon inducers. Also, a structurally unrelated class of low molecular weight interferoninducers, represented by a propanediamine, CP-20,961, and a xylylene-diamine, CP-28,888, was reported. The biological data available on both high and low molecular weight interferon inducers is becoming substantial and impressive in terms of antiviral, antitumor, and immunoregulatory effects.

Synthesis of a Gene Coding for Human Vasoactive Intestinal Peptide (VIP)

Abstract A gene coding for human Vasoactive Intestinal Peptide (VIP) was designed as a double-stranded 99 base pair DNA sequence. The sixteen fragments of the gene were chemically synthesized using a solid-phase phosphoramidite triester coupling approach and enzymatically assembled using T4 DNA ligase. The resulting gene was cloned into pBR322 and sequenced using the Maxam-Gilbert sequencing procedure.

Investigations of the mechanism of nucleoside synthesis. I. 13C-NMR studies of dihydro-s-triazine-SnCl4 complexes

Abstract 13C-NMR has been employed to demonstrate and define the nature of SnIV octahedral complexes of bissilyl triazines as a further investigation of nucleoside condensation mechanisms.