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B Samuelsson

Publications and source records attributed to B Samuelsson.

371 records · Page 21Linked to original sources
PubMedDate not supplied

Solid-phase synthesis of libraries generated from a 4-phenyl-2-carboxy-piperazine scaffold.

Strategies for finding novel structures of therapeutical interest are discussed. The rationale for the selection of the two scaffolds N4-(m-aminophenyl)-piperazine-2-carboxylic acid E and N4-(o-aminophenyl)-piperazine-2-carboxylic F is described. The synthesis of the appropriate precursors to scaffold E and F and their use in solid-phase chemistry are described. A 160-member library was produced combining these novel piperazine scaffolds with eight sulfonyl chlorides/acid chlorides and 10 amines. The compound library prepared was analyzed using LC-MS, showing the expected base peak in all wells at an average purity of 82%.

Calcium Channel Blockers↗
PubMedDate not supplied

Leukotriene A4 hydrolase: structural and functional properties of the active center.

Leukotriene (LT) A4 hydrolase (EC 3.3.2.6) is a bifunctional zinc metalloenzyme that possesses both an epoxide hydrolase activity, i.e., the well-known conversion of LTA4 into the proinflammatory substance LTB4, and a recently discovered peptidase activity. We have employed biochemical/kinetic analyses of native enzyme as well as site directed mutagenesis towards a recombinant enzyme to explore structural and functional properties of the enzyme active center. Thus, we have found that the peptidase activity is selectively stimulated by chloride ions, in a manner that suggests the presence of an anion binding site. Furthermore, a number of mutated enzymes have been constructed, expressed in E. coli, and purified to homogeneity to allow enzyme activity determinations and zinc analyses. The catalytic properties and zinc contents of these mutated enzymes establish the three zinc binding ligands of the protein and identify Glu-296 as a catalytic amino acid, directly involved in the peptidase, but not in the epoxide hydrolase reaction. In conclusion, our data provide strong evidence that the two catalytic activities of LTA4 hydrolase are exerted via non-identical but overlapping active sites.

Amino Acid Sequence↗