Enzymatic (2R,4R)-Pentanediol Synthesis – “Putting a Bottle on the Table”

(2R,4R)-Pentanediol is an interesting precursor for the synthesis of chiral ligands. A ketoreductase (KRED) was employed for the asymmetric reduction of acetylacetone to this diol. Biocatalysis often suffers from low concentrations of hydrophobic substrates and low stability of the enzyme in unconventional media. Here, we present an engineered KRED variant applicable in a neat substrate system, including upscaling to the multi-liter scale and downstream processing (DSP). Our engineered KRED applied in a neat substrate system is a powerful technique for the synthesis of chiral diols yielding product concentrations of 208 g L⁻¹.     

Human monoclonal antibodies to domain C of tenascin-C selectively target solid tumors in vivo

We had previously reported that splice isoforms of tenascin-C containing the extra-domain C are virtually absent in normal adult tissues but are highly abundant in high-grade astrocytomas, with a prominent peri-vascular pattern of expression. We now report that the extra-domain C of tenascin-C is strongly expressed in the majority of lung cancers, with a vascular and stromal pattern of expression. Using antibody phage technology, we have generated a human monoclonal antibody (G11), with a dissociation constant K(D) = 4.2 nM for the human domain C. The G11 antibody, expressed in scFv and in mini-antibody (SIP) format, as well as a scFv-interleukin-2 fusion protein, was then characterized in quantitative biodistribution studies using mice grafted subcutaneously with U87 gliomas, revealing a selective tumor uptake, with tumor/blood ratios up to 11.8:1 at 24 h. A radioiodinated preparation of SIP(G11) was also investigated in a double tracer study using an orthotopic rat glioma model, confirming the antibody's ability to preferentially localize at the tumor site, with tumor/brain ratios superior to the ones observed with (18)F-fluorodeoxyglucose. These tumor-targeting properties, together with the strong immunohistochemical staining of human tumor sections, indicate that the G11 antibody may be used as a portable targeting moiety for the selective delivery of imaging and therapeutic agents to gliomas and lung tumors.     

Fatigue Induced Alteration of the Superficial Strength Properties of 2024 Aluminum Alloy

Aircraft aluminum alloy 2024 T3 specimens have been subjected to constant amplitude fatigue loading at R=0.1. During fatigue, an appreciable increase of the surface hardness of the material at the meso-scale can be observed and captured by means of nanoindentations. Surface hardness increases with increasing fatigue stress amplitude and advancing number of applied fatigue cycles. Observed increase of specimen surface hardening degree during fatigue causes an evolution of superficial mechanical strength properties of the alloy. Stress-strain curves associated with the evoluting superficial mechanical properties are derived, employing a developed finite element method (FEM)-supported evaluation procedure of nanoindentation experimental results.