ABSTRACT
A three-step synthesis of benzo[c]thiophenes is presented in which the key transformation is the gold-catalyzed 5-exo-dig migratory cycloisomerization of a diallyl thioacetal. It was shown that a small amount of in situ generated HAuCl4 from AuCl3 is the active catalytic species. A mechanism was proposed.
Subject(s)
Benzene Derivatives/chemical synthesis , Chlorides/chemistry , Gold Compounds/chemistry , Thiophenes/chemical synthesis , Benzene Derivatives/chemistry , Catalysis , Cyclization , Isomerism , Thiophenes/chemistryABSTRACT
Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in ≥80% of recipients. Pf sporozoites (PfSPZ) administered by mosquito bites are the only immunogens shown to induce such protection in humans. Such protection is thought to be mediated by CD8(+) T cells in the liver that secrete interferon-γ (IFN-γ). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-specific CD8(+), IFN-γ-producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria.
Subject(s)
CD8-Positive T-Lymphocytes/immunology , Liver/immunology , Malaria Vaccines/immunology , Malaria, Falciparum/prevention & control , Plasmodium falciparum/immunology , Sporozoites/immunology , Adolescent , Adult , Animals , Antibodies, Protozoan/blood , Antibodies, Protozoan/immunology , Antigens, Protozoan/immunology , Humans , Injections, Intravenous , Injections, Subcutaneous , Interferon-gamma/biosynthesis , Interferon-gamma/immunology , Macaca mulatta , Malaria Vaccines/administration & dosage , Malaria Vaccines/adverse effects , Mice , Middle Aged , Rabbits , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/adverse effects , Vaccines, Attenuated/immunology , Young AdultABSTRACT
Ever since scientists discovered that conventional silicon-based computers have an upper limit in terms of speed, they have been searching for alternative media with which to solve computational problems. That search has led them, among other places, to DNA.
