Ibergirhynchia contraria (F. A. Roemer, 1850), an Early Carboniferous seep-related rhynchonellide brachiopod from the Harz Mountains, Germany - A possible successor to Dzieduszyckia?

A new genus Ibergirhynchia, a member of the rhynchonellide superfamily Dimerelloidea, is described for the species Terebratula contraria Roemer, 1850, from Early Carboniferous deposits of the Harz Mountains, Germany. Ibergirhynchia contraria is from a monospecific brachiopod limestone that formed on top of the drowned Devonian Iberg Reef which persisted as a seamount during Famennian and Early Carboniferous times. Ibergirhynchia contraria is considered a cold seep-related brachiopod based on this locality. Such seep associations have been observed for Mesozoic representatives of the rhynchonellide superfamily Dimerelloidea. Ibergirhynchia is considered the first Paleozoic representative of the family Rhynchonellinidae. Ibergirhynchia resembles Dzieduszyckia externally and may be derived from this dimerelloid.

Formal total synthesis of (±)-conduramine E utilising the Bryce-Smith-Gilbert photoamination reaction

Utilising a Bryce-Smith-Gilbert photoamination of benzene as a key step, a synthesis of ()-conduramine E was carried out. A highly regioselective dihydroxylation of a cyclic diene was effected utilising Sharpless AD-mix-b.

Trapping of palindromic ligands within native transthyretin prevents amyloid formation

Transthyretin (TTR) amyloidosis is a fatal disease for which new therapeutic approaches are urgently needed. We have designed two palindromic ligands, 2,2’-(4,4’-(heptane 1,7-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (mds84) and 2,2’-(4,4’-(undecane-1,11-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (4ajm15), that are rapidly bound by native wild-type TTR in whole serum and even more avidly by amyloidogenic TTR variants. One to one stoichiometry, demonstrable in solution and by MS, was confirmed by X-ray crystallographic analysis showing simultaneous occupation of both T4 binding sites in each tetrameric TTR molecule by the pair of ligand head groups. Ligand binding by native TTR was irreversible under physiological conditions, and it stabilized the tetrameric assembly and inhibited amyloidogenic aggregation more potently than other known ligands. These superstabilizers are orally bioavailable and exhibit low inhibitory activity against cyclooxygenase (COX). They offer a promising platform for development of drugs to treat and prevent TTR amyloidosis.