No abstract

The synthesis of a series of 2-anilinophenylacetic acids, close analogues of diclofenac, is described. These compounds were tested in two models used for evaluating the activity of nonsteroidal antiinflammatory drugs (NSAID's), inhibition of cyclooxygenase enzyme activity in vitro, and adjuvant-induced arthritis (AdA) in rats. Statistically significant correlations were found between the inhibitory activities of the compounds in these two models, indicating that cyclooxygenase inhibition seems to be the underlying mechanism for the antiinflammatory activity of these compounds. Quantitative structure-activity relationship (QSAR) analysis revealed that the crucial parameters for activity in both models were the lipophilicity and the angle of twist between the two phenyl rings. Optimal activities were associated with halogen or alkyl substituents in both ortho positions of the anilino ring. Compounds with OH groups in addition to two ortho substituents or compounds with only one or no ortho substituents were less active.

No abstract

The amino acid sequence of the single polypeptide chain of bovine plasminogen (786 residues, M , 88092) was determined. Cleavage with CNBr yielded 13 fragments of which six originated from cleavage sites different from human plasminogen. Digestion with elastase gave three major fragments: kringles (1 + 2 + 3) and kringle 4, both with intact lysine binding sites, and mini-plasminogen. Subfragmentation was achieved mainly with 2-(2-nitrophenylsulfenyl)-3-methyl-3'-bromoindolenine (BNPS-skatole), Staphylococcus aweus V8 protease and trypsin. The sequences of fragments which were determined by automated Edman degradation, were aligned with overlapping sequences, or, in a few instances, by homology with the known sequence of human plasminogen. Sequence comparison with the human protein showed varying degrees of homology in the different functional and structural domains. The overall identity (78%) is practically the same as that found in those regions corresponding to the heavy (79%) and the light chain (80%) of plasmin. The average degree of identity among the kringles is 83%. Outside the kringle structures the extent of identity decreases, to 65% in the N-terminal region and to about 50% in the connecting strands between the kringles except for the strand between kringles 2 and 3, where only one out of 12 residues is exchanged. The results reported show that bovine plasminogen apparently contains the same structural and functional domains as human plasminogen.