Anti-SPR monoclonal antibody, clone 4D9

A reflective optical sensor based on surface plasmon resonance (SPR) was proposed to measure the glucose concentration. The gold film was sputtered on the surface of plastic cladding optical fiber to excite SPR and reflect light at the same time, making the SPR sensor highly sensitive to the variation of surrounding refractive index. Then, glucose oxidase (GOD) was adopted as the sensitive film of glucose and covalently bonded on the gold film. The enzymatic reaction between the GOD and the glucose led to the change of refractive index around the optical fiber sensor, and then cause a shift of the SPR spectrum. Therefore, the glucose concentration could be obtained by monitoring the shift of the resonance wavelength. Experimental results showed that the measurement sensitivity of the SPR sensor could reach 85.4 nm/(mg/mL) (for glucose concentration) with good selectivity and stability, which has great potential application in biomedicine and human health monitoring.

The majority of chronic myeloid leukemia (CML) cases are caused by a chromosomal translocation linking the breakpoint cluster region (BCR) gene to the Abelson murine leukemia viral oncogene-1 (ABL1), creating the mutant fusion protein BCR-ABL1. Downstream of BCR-ABL1 is growth factor receptor-bound protein-2 (GRB2), an intracellular adapter protein that binds to BCR-ABL1 via its src-homology-2 (SH2) domain. This binding constitutively activates growth pathways, downregulates apoptosis, and leads to an over proliferation of immature and dysfunctional myeloid cells. Utilizing novel synthetic methods, we developed four furo-quinoxaline compounds as GRB2 SH2 domain antagonists with the goal of disrupting this leukemogenic signaling. One of the four antagonists, NHD2-15, showed a significant reduction in proliferation of K562 cells, a human BCR-ABL1(+)leukemic cell line. To elucidate the mode of action of these compounds, various biophysical,in vitro, andin vivoassays were performed. Surface plasmon resonance (SPR) assays indicated that NHD2-15 antagonized GRB2, binding with aK(D)value of 119 +/- 2 mu M. Cellulose nitrate (CN) assays indicated that the compound selectively bound the SH2 domain of GRB2. Western blot assays suggested the antagonist downregulated proteins involved in leukemic transformation. Finally, NHD2-15 was nontoxic to primary cells and adult zebrafish, indicating that it may be an effective clinical treatment for CML.