We report a method based on mass spectrometry for the characterization of noncovalent complexes of proteins with mixtures of ligands; this method is relevant to the study of drug leads and may be useful in screening libraries for tight-binding compounds. It is based on the ability of electrospray ionization (ESI)* 1•2 3to generate ions of intact noncovalent complexes in the gas phase3-5 and of Fourier transform ion cyclotron resonance

This paper describes the use of electrospray ionization-mass spectrometry (ESI-MS) to screen two libraries of soluble compounds to search for tight binding inhibitors for carbonic anhydrase II (EC 4.2.1.1). The two libraries, H2NO2SC6H4C(O)NH-AA1-AA2-C(O)NHCH2CH2CO2H where AA1 and AA2 are L-amino acids (library size: 289 compounds) or D-amino acids (256 compounds), were constructed by attaching tripeptides to the carboxyl group of 4-carboxybenzenesulfonamide. Screening of both libraries yielded, as the tightest binding inhibitor, compound 1 (AA1 = AA2 = L-Leu; binding constant Kb = 1.4 x 10(8) M-1). The ability of ESI-MS to estimate simultaneously the relative binding affinities of a protein to soluble ligands in a library, if general, should be useful in drug development.

The circulation associated with extreme heat (EH) typically shows an anomalous anticyclone that enhances temperature through adiabatic heating, but this study indicates obvious spatial variation in eastern China. The EH-related circulation pattern in eastern China can be classified into three categories: typical extratropical pattern, monsoonal pattern, and foehn pattern. EH over northeastern China and eastern north China is characterized by a typical pattern involving an anomalous anticyclone and subsidence, and the air temperature increases throughout almost the entire troposphere. In contrast, EH over the Yangtze River valley and south China is associated with the monsoonal pattern. Over these regions, the air temperature only increases in the lower troposphere as a result of anomalous subsidence and lower humidity that has resulted from a farther north transportation of water vapor by a stronger monsoonal southwesterly. Meanwhile, the air temperature decreases in the upper troposphere because of the decrease of latent heat caused by suppressed precipitation. On the other hand, western north China, with most of its stations located on the eastern leeside of mountains, is obviously influenced by the foehn effect on EH days. The foehn-related northwesterly anomalies bring drier and warmer air from the mountains to sink on the leeside and greatly increase the air temperature in the lower troposphere, particularly near the surface. Therefore, the impacts of monsoon and topography should be taken into consideration when EH-related circulations are discussed over the many regions of eastern China. As a result, the reliable projection of air temperature in these regions under global warming is a challenging problem.