Isolation Of New Members Research Articles

Gausemycin Antibiotic Family Acts via Ca2+-Dependent Membrane Targeting.

We report the molecular mechanism of action of gausemycins and the isolation of new members of the family, gausemycins C (1c), D (1d), E (1e), and F (1f), the minor components of the mixture. To elucidate the mechanism of action of gausemycins, we investigated the antimicrobial activity of the most active compounds, gausemycins A and B, in the presence of Ca2+, other metal ions, and phosphate. Gausemycins require a significantly higher Ca2+ concentration for maximum activity than daptomycin but lower than that required for malacidine and cadasides. Species-specific antimicrobial activity was found upon testing against a wide panel of Gram-positive bacteria. Membranoactivity of gausemycins was demonstrated upon their interactions with model lipid bilayers and micelles. The pore-forming ability was found to be dramatically dependent on the Ca2+ concentration and the membrane lipid composition. An NMR study of gausemycin B in zwitterionic and anionic micelles suggested the putative structure of the gausemycin/membrane complex and revealed the binding of Ca2+ by the macrocyclic domain of the antibiotic.

Recent Progress in the Chemistry of Daphniphyllum Alkaloids †.

Daphniphyllum is an evergreen species known since 1826. After initial systematic investigations, more than 320 members of this family have been isolated, which comprise complex and fascinating structures. Unique azapolycyclic architectures containing one or more quaternary stereocenters render these alkaloids synthetically challenging. This review covers efforts toward the synthesis of Daphniphyllum alkaloids spanning the period from 2005 to the beginning of 2016, including reported biological activities as well as the isolation of new members of this genus.

Ligand regulation of retinoic acid receptor-related orphan receptors: implications for development of novel therapeutics

In the late 1980s, the cloning of several nuclear receptors led to the intense search and isolation of new members of this superfamily. Despite their identification, many of these receptors were dubbed 'orphan' receptors, as their physiological ligands remained unknown. Recent reports have presented evidence for one family of orphan receptors, the retinoic acid receptor-related orphan receptors (RORs), in several pathologies, including osteoporosis, several autoimmune diseases, asthma, cancer, diabetes and obesity. The present review summarizes the studies identifying ligands for the RORs and evaluates their role as targets for potential therapeutics. Significant progress was made in the initial identification of ligands for the RORs when X-ray crystallographic studies identified several molecules within the ligand-binding pockets of RORalpha and RORbeta. Recently, we identified endogenous and synthetic ligands for RORalpha and RORgamma, thereby solidifying their function as ligand-dependent transcription factors. Recent studies have established roles for the RORs in physiological development and the advent of disease. Identification of ligands for the RORs, both endogenous and synthetic, has established these receptors as attractive new therapeutic targets for the treatment of ROR-related diseases.

Chapter 2 Cloning and analysis of Bcl-2 family genes

Publisher Summary This chapter reviews the Bcl-2 family, describing characteristics used for the isolation of new members. The chapter provides an overview of how several Bcl-2 homologs are isolated, cloned, and characterized. The chapter discusses the functional assays used to test Bcl-2 function and regulation. The Bcl-2 family of proteins regulates cell death by either inducing or inhibiting apoptosis. The antiapoptotic subfamily includes Bcl-2, Bcl-X L , Bcl-w, Mcl-1, A1, NR-13, and CED-9. When over expressed, these proteins protect the cells from apoptotic stimuli, such as growth factor withdrawal, irradiation, DNA-damaging agents, and some death receptor signals. The Bax subfamily includes Bax, Bak, and Bok. The BH3-only subfamily includes Bik, Blk, Hrk, BimL, Bad, Bid, and EGL-1. Both the Bax and BH3- only subfamilies, induce apoptosis when over expressed. Moreover, the presence of conserved BH domains among Bcl-2 family members has allowed the identification and cloning of several Bcl-2 family members at the DNA level by low stringency DNA hybridization, PCR, and database searches. By understanding the differences in BH domains between Bcl-2 subfamilies, future searches for novel Bcl-2 family members can be directed toward a specific activity.

Finding new genes in the nervous system by cDNA analysis

There are several methods to isolate c DNAs that do not require prior biochemical characterization of their protein products, including isolation of new members of particular protein families based on sequences of known members, selection of specific clones by differential screening, and shotgun analysis of a particular c DNA population. This third approach will produce a huge catalogue of c DNA sequences and anatomical data that will be useful to investigators with diverse interests. Recent methodological advances allow c DNAs to be isolated and sequenced rapidly. These methods, coupled with fast and reliable techniques for in situ hybridization histochemistry, should permit c DNA catalogues to be assembled efficiently.

Separation of polythiadioxopiperazine antibiotics by thin-layer chromatography

Abstract : In recent years the number of 2,5-epipolythia-3,6-dioxopiperazine antibiotics has increased significantly due to isolation of new members of the series and by chemical transformations of the naturally-occurring compounds. By extensive chemical and/or X-ray crystallographic investigations the structure of gliotoxin (I), sporidesmin (II, X = 2, R = OH) and dehydrogliotoxin (III, X = 2) was determined and other closely related compounds have since been isolated or synthesized. The report deals with the thin-layer chromatographic behavior of fifteen of these sulfur-containing compounds. The separation of polysulfides (II, X = 1, 2, 3, 4, R = OH) and (III, X = 1, 2, 3, 4) differing only in the number of sulfur atoms in the 2,5 bridge is particularly noted. (Author)