STRUCTURE-ACTION RELATIONSHIPS OF CORTICOSTEROID COMPOUNDS AS INHIBITORS OF LEUKEMIC L5187Y CELL REPRODUCTION IN VIVO AND IN VITRO.

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Abstract Not Available

Action of Cisplatin (cis-dichlorodiammine platinum II) and Poly-Plat [poly-[(trans-1,2-diaminocyclohexane) pla-tinum]-carboxyamylose] on tumor cells was examined using human fibrosarcoma (HT1080) and Walker rat carcinoma (WRC-256) in culture. These cells were treated with Poly-Plat (10 microg/ml) or Cisplatin (10 mg/ml) for 2-5 days. Peritoneal macrophages were treated with Cisplatin (10 microg/ml) or Poly-Plat (10 microg/ml) for 2 hours and allowed to grow in normal medium for 48 hours. Supernatants from treated macrophages were collected at 0...

Thrombin is a multifunctional serine proteinase that plays a key role in coagulation while exhibiting several other key cellular bioregulatory functions. The X-ray crystal structure of human alpha-thrombin was determined in its complex with the specific thrombin inhibitor D-Phe-Pro-Arg chloromethylketone (PPACK) using Patterson search methods and a search model derived from trypsinlike proteinases of known spatial structure (Bode, W., Mayr, I., Baumann, U., Huber, R., Stone, S.R., & Hofsteenge, J., 1989, EMBO J. 8, 3467-3475). The crystallograp...

An increase in the opportunistic fungal infections necessitates a design of new more effective and safer antifungal agents. Triazole alcohols are effective antifungals, but have a risk of teratogenicity associated with them. Therefore, successful design of drugs from this class depends on understanding the structure-activity and structure-teratogenicity relationships in conjunction. To this end, we applied the Multiple Computer-Automated Structure Evaluation (Multi-CASE) methodology to a study of the relationships between the structures of 71 t...

Bacterial class I release factors (RFs) are seen by cryo-electron microscopy (cryo-EM) to span the distance between the ribosomal decoding and peptidyl transferase centers during translation termination. The compact conformation of bacterial RF1 and RF2 observed in crystal structures will not span this distance, and large structural rearrangements of RFs have been suggested to play an important role in termination. We have collected small-angle X-ray scattering (SAXS) data from E. coli RF1 and from a functionally active truncated RF1 derivative...

Ornithine decarboxylase (ODC) is a pyridoxal 5'-phosphate (PLP) dependent homodimeric enzyme. It is a recognized drug target against African sleeping sickness, caused by Trypanosoma brucei. One of the currently used drugs, alpha-difluoromethylornithine (DFMO), is a suicide inhibitor of ODC. The structure of the T. brucei ODC (TbODC) mutant K69A bound to DFMO has been determined by X-ray crystallography to 2.0 A resolution. The protein crystallizes in the space group P2(1) (a = 66.8 A, b = 154.5 A, c = 77.1 A, beta = 90.58 degrees ), with two di...

The solution structure of the 64 amino acid Fe4S4 ferredoxin I from Desulfovibrio africanus has been determined using two-dimensional 1H NMR spectroscopy. Sequence-specific assignments were obtained for 59 amino acid residues and the structure determined with the program DIANA on the basis of 549 nuclear Overhauser enhancement (NOE) upper distance limits, and four dihedral angle and 52 distance constraints for the Fe4S4 cluster. The NMR structure was refined using the simulated annealing and energy minimisation protocols of the program X-PLOR t...

A series of peptidomimetic human immunodeficiency virus (HIV) protease inhibitors containing substituted all-phenylnorstatine [APNS: (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid] were designed and synthesized. From the structure-metabolism relationship of this type of HIV protease inhibitors, the compounds having para substitution of the phenyl ring of Apns and/or 2,6-disubstitution of the P2' benzylamine were found to be able to avoid the P2 phenol glucuronidation that occurs with SM-319777 (formerly named JE-2147, KNI-764); one of the main ...