Hydrophobic benzyl amines as supports for liquid-phase C-terminal amidated peptide synthesis: application to the preparation of ABT-510.

C-terminal amidation is one of the most common modification of peptides and frequently found in bioactive peptides. However, the C-terminal modification must be creative, because current chemical synthetic techniques of peptides are dominated by the use of C-terminal protecting supports. Therefore, it must be carried out after the removal of such supports, complicating reaction work-up and product isolation. In this context, hydrophobic benzyl amines were successfully added to the growing toolbox of soluble tag-assisted liquid-phase peptide synthesis as supports, leading to the total synthesis of ABT-510 (2). Although an ethyl amide-forming type was used in the present work, different types of hydrophobic benzyl amines could also be simply designed and prepared through versatile reductive aminations in one step. The standard acidic treatment used in the final deprotection step for peptide synthesis gave the desired C-terminal secondary amidated peptide with no epimerization.

[Lupus anticoagulant-hypoprothrombinemia syndrome with a false-positive test for coagulation factor inhibitors].

We report a case of a 1-year-old boy diagnosed with lupus anticoagulant-hypoprothrombinemia syndrome (LA-HPS), which is a rare disorder. His initial presentation of sinusitis was accompanied by hemorrhagic episodes including ecchymoses and epistaxis 6 months after antibiotic therapy. Laboratory results revealed prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT) that did not correct with mixing studies. Factors II, VIII, IX, X, XI, and XII activities were 20%, 44%, 42.5%, 59%, 4%, and 10%, respectively. The Bethesda inhibitor assay showed inhibitors against multiple coagulation factor. APTT, mixing studies, diluted Russell's viper venom time, and the Bethesda inhibitor assay detected LA. LA-HPS with a suspected false-positive test for coagulation factor inhibitors was diagnosed. Bleeding stopped and results of coagulation studies returned to normal without therapy 2 months after onset of the disease.

Estimation of the contribution of ultrafine particles to lung deposition of particle-bound mutagens in the atmosphere.

The present study was performed to estimate the contributions of fine and ultrafine particles to the lung deposition of particle-bound mutagens in the atmosphere. This is the first estimation of the respiratory deposition of atmospheric particle-bound mutagens. Direct and S9-mediated mutagenicity of size-fractionated particulate matter (PM) collected at roadside and suburban sites was determined by the Ames test using Salmonella typhimurium strain TA98. Regional deposition efficiencies in the human respiratory tract of direct and S9-mediated mutagens in each size fraction were calculated using the LUDEP computer-based model. The model calculations showed that about 95% of the lung deposition of inhaled mutagens is caused by fine particles for both roadside and suburban atmospheres. Importantly, ultrafine particles were shown to contribute to the deposition of mutagens in the alveolar region of the lung by as much as 29% (+S9) and 26% (-S9) for the roadside atmosphere and 11% (+S9) and 13% (-S9) for the suburban atmosphere, although ultrafine particles contribute very little to the PM mass concentration. These results indicated that ultrafine particles play an important role as carriers of mutagens into the lung.

Bioremediation of the organochlorine pesticides, dieldrin and endrin, and their occurrence in the environment.

Dieldrin and endrin are persistent organic pollutants that cause serious environmental problems. Although these compounds have been prohibited over the past decades in most countries around the world, they are still routinely found in the environment, especially in the soil in agricultural fields. Bioremediation, including phytoremediation and rhizoremediation, is expected to be a useful cleanup method for this soil contamination. This review provides an overview of the environmental contamination by dieldrin and endrin, along with a summary of our current understanding and recent advances in bioremediation and phytoremediation of these pollutants. In particular, this review focuses on the types and abilities of plants and microorganisms available for accumulating and degrading dieldrin and endrin.

Isolation of dieldrin- and endrin-degrading bacteria using 1,2-epoxycyclohexane as a structural analog of both compounds.

This report describes the selective isolation of dieldrin- and endrin-degrading bacteria from soil with high degradation activity toward dieldrin and endrin. Several enrichment cultures from the soil were arranged with several structural analogs of dieldrin and endrin as a growth substrate and examined for their degradation activities toward dieldrin and endrin. An enrichment culture with 1,2-epoxycyclohexane (ECH) was found to aerobically degrade dieldrin and endrin. Denaturing gradient gel electrophoresis (DGGE) indicated that three types of bacteria were predominant in the ECH enrichment culture. Of the three major bacteria, two isolates, Burkholderia sp. strain MED-7 and Cupriavidus sp. strain MED-5, showed high degradation activity toward dieldrin and endrin. The degradation efficiencies of strain MED-7 and MED-5 were 49% and 38% toward dieldrin, respectively, and 51% and 40% toward endrin, respectively, in the presence of ECH for 14 days. These results indicated that ECH was a useful substrate for selective and efficient isolation of dieldrin- and endrin-degrading bacteria from soil containing numerous bacteria. Interestingly, the two isolates could also degrade dieldrin and endrin even in the absence of ECH. These are the first microorganisms demonstrated to grow on dieldrin and endrin as the sole carbon and energy source under aerobic conditions.