Syntheses of Novel Biologically Active Compounds Utilizing Countesactive Action in diving Body and their Clinical Trials

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Novel steroids, hemisuccinyl methyl glycolates were prepared from the corresponding methyl glycolates derived from predonisolone and dexamethasone based on a concept of the antedrug. Their topical anti-inflammatory activity was evaluated through croton-induced ear edema and paper disk granuloma bioassay. Two (20S)-succinyl dexamethasone derivatives indicated more potent anti-inflammatory activity than the parent compounds and did not show corticosteroidal side effects of thymic, adrenal involution or body weight loss due to easy conversion of the succinyl derivatives into active compounds followed by rapid elimination from the circulation system in the rat. From these results, these two derivatives might be candidates as the novel steroids without the systemic side effects of corticosteroids.On the other hand, we tried to isolate the neutralizing human antibody against verotoxin (VT), which is an enterotoxin produced from Escherichia coli, O157-H7. We constructed human antibody combinatorial library from PBL of the O157-postinfected donor. We selected three VT1-reactive rFab clones and two VT2-reactive rFab clones from the antibody combinatorial antibody panning against VTs. These clones were found to be cross-reactive with another type of VT, and showed no neutralizing activity against VTs. These results suggest that isolated clones would recognize the neutralization-unrelated epitope commonly presented in both VT1 and VT2.