A comparison of HER2/neu accumulations of Ga-67-labeled anti-HER2 antibody with chemically and site-specifically conjugated bifunctional chelators.

Monoclonal antibodies (mAb) developed to target specific cancers have achieved considerable success to date. To further enhance therapeutic efficacy, monoclonal antibodies may be conjugated with a cytotoxic drug or radioisotope. We present the development of a new method based on site-specific conjugation (SSC) for targeting HER2. The study design involves a comparison of the accumulation of Ga-67-labeled anti-HER2 antibodies with SSC (SSC-mAb) versus conventional chemical conjugation (Chem-mAb) in HER2-positive tumors. In vitro, the HER2-binding capacity of SSC-mAb and Chem-mAb was comparable. However, in vitro, the rate of tumor accumulation increased gradually with SSC-mAb not only in the tumors but also in the blood and other organs. The SSC may improve targeted antigen-specific cancer radioimmunotherapy and may, due to higher retention, reduce the amount of treatment required.

Amino Acid Schiff Base Bearing Benzophenone Imine As a Platform for Highly Congested Unnatural α-Amino Acid Synthesis.

Unnatural α-amino acids are invaluable building blocks in synthetic organic chemistry and could upgrade the function of peptides. We developed a new mode for catalytic activation of amino acid Schiff bases, serving as a platform for highly congested unnatural α-amino acid synthesis. The redox active copper catalyst enabled efficient cross-coupling to construct contiguous tetrasubstituted carbon centers. The broad functional group compatibility highlights the mildness of the present catalysis. Notably, we achieved successive ß-functionalization and oxidation of amino acid Schiff bases to afford dehydroalanine derivatives bearing tetrasubstituted carbon. A three-component cross-coupling reaction of an amino acid Schiff base, alkyl bromides, and styrene derivatives demonstrated the high utility of the present method. The diastereoselective reaction was also achieved using menthol derivatives as a chiral auxiliary, delivering enantiomerically enriched α-amino acid bearing α,ß-continuous tetrasubstituted carbon. The synthesized highly congested unnatural α-amino acid could be derivatized and incorporated into peptide synthesis.

An Expeditious Route to trans-Configured Tetrahydrothiophenes Enabled by Fe(OTf)3 -Catalyzed [3+2] Cycloaddition of Donor-Acceptor Cyclopropanes with Thionoesters.

A synthetic route to trans-configured tetrahydrothiophenes (THTs) through Fe(OTf)3 -promoted [3+2] cycloaddition of donor-acceptor cyclopropanes with thionoesters was developed. The cycloaddition proceeded in high yield with high diastereoselectivity, affording transient α-alkoxy THTs. Not only aromatic and aliphatic thionoesters, but also thionolactone were applicable to the present iron catalysis. Further transformation of the S,O-ketal functionality of the product was achieved in a highly trans diastereoselective manner. Moreover, the utility of our methodology was clearly demonstrated by the synthesis of enantioenriched trans-configured THTs.

Dynamic surface tension and surface dilatational elasticity properties of mixed surfactant/protein systems.

We present the study on dynamic surface tension and surface dilatational elasticity properties of dilute aqueous systems of pentaglycerol fatty acid esters (pentaglycerol monostearate, C18G5, and pentaglycerol monooleate, C18:1G5, whey protein, sodium caseinate, and mixed surfactant and protein at room temperature. The adsorption kinetics at the air-liquid interface has been studied by bubble pressure tensiometer and the oscillation bubble (rising drop) method. It has been shown that the dynamic surface tension curve basically presents two-regions; namely induction region and rapid fall region. During the induction time the adsorption is the diffusion-controlled process of amphiphilic surfactant or protein molecules from the bulk of the solution to the interface. Whey protein and sodium caseinate showed longer induction time approximately 10000 ms compared to the surfactant systems, where induction time was estimated to be approximately 1000 ms. However, in both the protein and surfactant systems, the induction time goes on decreasing with increasing the concentrations. The similar behavior was observed in the mixed system, and lower surface tension values were observed at higher concentrations. The fitting of the experimental data to the theoretical equation shows the presence of two relaxation mechanisms of widely different time scale for the adsorption of surfactant or protein molecules at the interface. The relaxation time strongly varies with the concentrations following the power law, and at fixed concentration it was the highest for whey protein and the lowest for C18:1G5 system. The surface dilatational elasticity determined within the frequency range of approximately 0.1 to 1 cycle/s supports the dynamic surface tension data.