Total Synthesis and Structure Correction of the Cyclic Lipodepsipeptide Orfamide A.

A total synthesis of the cyclic lipodepsipeptide natural product orfamide A was achieved. By developing a synthesis format using an aminoacid ester building block and SPPS protocol adaptation, a focused library of target compounds was obtained, in high yield and purity. Spectral and LC-HRMS data of all library members with the isolated natural product identified the Leu residue to be d- and the 3'-OH group to be R-configured.

Enzyme-Primed Native Chemical Ligation Produces Autoinducing Cyclopeptides in Clostridia.

Clostridia coordinate many important processes such as toxin production, infection, and survival by density-dependent communication (quorum sensing) using autoinducing peptides (AIPs). Although clostridial AIPs have been proposed to be (thio)lactone-containing peptides, their true structures remain elusive. Here, we report the genome-guided discovery of an AIP that controls endospore formation in Ruminiclostridium cellulolyticum.

Synthesis and catalytic activity of tridentate N-(2-pyridylethyl)-substituted bulky amidinates of calcium and strontium.

Metalation of the formamidine Dipp-N[double bond, length as m-dash]C(H)-N(H)-C2H4-Py (1a) and benzamidine Dipp-N[double bond, length as m-dash]C(Ph)-N(H)-C2H4-Py (1b) with [(thf)2M{N(SiMe3)2}2] (M = Ca, Sr) yields the corresponding homoleptic complexes [M{Dipp-N[double bond, length as m-dash]C(R)-N-C2H4-Py}2] (M/R = Ca/H (2a), Ca/Ph (2b), and Sr/Ph (3b)) regardless of the applied stoichiometry. Only during calciation of Dipp-N[double bond, length as m-dash]C(H)-N(H)-C2H4-Py (1a), the heteroleptic intermediate [{(Me3Si)2N}Ca{Dipp-N[double bond, length as m-dash]C(R)-N-C2H4-Py}]2 (2a') has been observed. The formamidinate complex of strontium crystallizes as a tmeda adduct of the type [(tmeda)Sr{Dipp-N[double bond, length as m-dash]C(H)-N-C2H4-Py}2] (3a).

Structure Elucidation and Activity of Kolossin A, the D-/L-Pentadecapeptide Product of a Giant Nonribosomal Peptide Synthetase.

The largest continuous bacterial nonribosomal peptide synthetase discovered so far is described. It consists of 15 consecutive modules arising from an uninterrupted, fully functional gene in the entomopathogenic bacterium Photorhabdus luminescens. The identification of its cryptic biosynthesis product was achieved by using a combination of genome analysis, promoter exchange, isotopic labeling experiments, and total synthesis of a focused collection of peptide candidates.

Phthalate exposure in pregnant women and newborns - the urinary metabolite excretion pattern differs distinctly.

Some phthalates are endocrine disruptors and reproductive and developmental toxicants. Data on newborn phthalate exposure and elimination characteristics are scarce. We determined 21 urinary phthalate metabolites (indicating exposure to 11 parent phthalates) in two study approaches: in the first approach we collected the urine of 20 healthy newborns at days 2-5 post partum together with 47 urine samples of 7 women during pregnancy.

Fatty acid distribution of cord and maternal blood in human pregnancy: special focus on individual trans fatty acids and conjugated linoleic acids.

Background: Maternal nutrition in pregnancy has a crucial impact on the development of the fetus. Dietary trans fatty acids (tFA) are known to have adverse health effects, especially during pregnancy. However, the distribution of tFA produced via partial hydrogenation of vegetable oils (mainly elaidic acid; t9) differs compared to ruminant-derived tFA (mainly vaccenic acid; t11).

Cell-specific RNA interference by peptide-inhibited-peptidase-activated siRNAs.

The use of chemically-synthesized short interfering RNAs (siRNAs) is the key method of choice to manipulate gene expression in mammalian cell cultures and in vivo. Several previous studies have aimed at inducing cell-specific RNA interference (RNAi) in order to use siRNA molecules as therapeutic reagents. Here, we used peptide-inhibited siRNAs that were activated after cleavage by cell-specific peptidases.

Development of a human model to study homing behavior of immune cells into decidua and placental villi under ex vivo conditions.

Problem: Homing of lymphocytes and NK cells into the decidua and its regulation has been very controversially discussed. Therefore, we aimed to establish an in vivo simulation method for analysis of homing behavior, which might be also useful for other cells such as stem or tumor cells.

Method Of Study: A human term placenta has been perfused with medium to elute blood and then with maternal autologous carboxyfluorescein succinimidyl ester (CFSE)-labeled peripheral blood lymphocytes for 3 hr and rinsed for another 2 hr.

Assessment of caspase-4 released free AFC by RP-HPLC and fluorescence detection.

A simple RP-HPLC method based on fluorescence detection was developed for the quantitation of 7-amino-4-trifluoro methylcoumarin (AFC) in cell lysates from JEG-3 choriocarcinoma cells for determination of caspase-4 activity. In contrast to the established methods of AFC detection using a fluorescence microplate reader or using a fluorescence photometer, the separation of AFC-signals from interfering fluorescence signals by a reversed phase column affords more precise quantitation of released AFC. This can be important for analyses of cell lysates with low caspase activity or experimental series with marginal differences among samples.

Impact of PUFA on early immune and fetal development.

It has recently been reported that the increased prevalence in childhood allergy may be linked to deviations in fetal immune development. One reason may be impaired nutrient supply. Hence, a well-differentiated placenta together with an optimal fetal nutrition via the mother are important prerequisites for the establishment of a functional immune system with normal immune responses.

Lessons from reproductive immunology for other fields of immunology and clinical approaches.

Reproduction is indispensable to evolution and, thus, life. Nonetheless, it overcomes common rules known to established life. Immunology of reproduction, and especially the tolerance of two genetically distinct organisms and their fruitful symbiosis, is one of the most imposing paradox of life.