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The specific association of an SH2 domain with a phosphotyrosine (pTyr)-containing sequence of another protein precipitates a cascade of intracellular molecular interactions (signals) which effect a wide range of intracellular processes. The nonreceptor tyrosine kinase Src, which has been associated with breast cancer and osteoporosis, contains an SH2 domain. Inhibition of Src SH2-phosphoprotein interactions by small molecules will aid biological proof-of-concept studies which may lead to the development of novel therapeutic agents. Structure-based design efforts have focused on reducing the size and charge of Src SH2 ligands while increasing their ability to penetrate cells and reach the intracellular Src SH2 domain target. In this report we describe the synthesis, binding affinity, and Src SH2 cocrystal structure of a small, novel, nonpeptide, urea-containing SH2 domain ligand.

The performance of a planar differential mobility spectrometer (DMS) is investigated when operated in air at ambient pressure and driven by a rectangular asymmetric waveform, limited to frequencies of <1.2 MHz and voltage pulse amplitudes of <1 kV with steep rise times of the order of approximately 15 ns. Independent control of frequency, voltage pulse amplitude, and duty cycle allow for characterizing the DMS in terms of transmission, resolution and separation. The tradeoff between sensitivity and resolution and the effect of duty cycle on instrument performance are demonstrated experimentally. The dependence of ion mobility on the magnitude of the electric field determines the displacement of ions measured by the DC compensation voltage as a function of the duty cycle. Optimum values for the duty cycle exist for the separation of A- and C-type ions, while, B-type ions exhibit a more complex behavior. An analytical expression for describing the effect of duty cycle on the separation of the ions, determined by variations in the compensation voltage, is developed and compared to experimental results obtained in air below 75 Td using estimated alpha parameters for a set of ketones. In this context, errors associated with the calculation of alpha parameters using polynomials of even powers are highlighted.

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