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Biomedical subjects

J Kakinuma

Publications and source records attributed to J Kakinuma.

8 recordsLinked to original sources
PubMed1998

A transcription frame-based analysis of the genomic DNA sequence of a hyper-thermophilic archaeon for the identification of genes, pseudo-genes and operon structures.

An algorithm for identifying transcription units, independently regulated genes and operons, and pseudo-genes that are not expected to be expressed, has been developed by combining a system for predicting transcription and translation signals, and a system for scoring the triplet periodicity in ORF candidates. By using the algorithm, the 1.09 Mb sequence that covers approximately 60% of the genome of Pyrococcus sp. OT3 has been analyzed. The identified ORFs show the expected biological and physical characteristics, while the rejected ORF candidates do not. Frequent use of operon structures for transcription, and gene duplication followed by mutation or termination of the duplicated genes, are discussed.

Base Composition↗
PubMed1997

Use of a 3D structure data base for understanding sequence-dependent conformational aspects of DNA.

The roll-twist-slide correlation in the DNA crystal structures that are collected in the Nucleic Acid Data Base is analyzed in order to obtain a general understanding of the effects of the nucleotide sequence on the 3D structure of a dinucleotide step. It is concluded that the differences between the pyrimidine bases and the purine bases in terms of their physical shapes are the major factors that determine the stereochemical characteristics of the steps through base to backbone and base to base interactions. The characteristics are further modulated by the differences between the A:T and G:C base-pairs, which can be explained by enhancement of the purine-pyrimidine asymmetry in the A:T base-pair.

Computational Biology↗
PubMed1997

DNA recognition by beta-sheets.

The modes of DNA recognition by beta-sheets are analyzed by using the known crystal and solution three-dimensional structures of DNA-protein complexes. Close fitting of the protein surface and the DNA surface determines the binding geometry. Interaction takes place so that essentially the N-to-C direction of the beta-strands either follows or crosses the DNA groove. Upon following the major groove a two-stranded antiparallel beta-sheet dives into the groove and contacts DNA bases with its convex side facing the DNA, while upon following the minor groove, it binds around the sugar-phosphate backbones, with its opposite concave side shielding the DNA. In order for the beta-strands crossing the minor groove to interact with the DNA, the dinucleotide steps need to almost totally helically untwist and roll around major groove. The beta-sheet, on the other hand, needs to adopt a concave curvature on the binding surface in the direction that follows the DNA minor groove, and a convex surface in the direction that bridges the sugar-phosphate backbones across the groove. The result is to produce a hyperbolic paraboloidal DNA-binding surface.

Amino Acid Sequence↗
PubMed1982

[Tumor affinity and DNA interactions of 57Co-bleomycin (author's transl)].

Cobalt-57-bleomycin (BLM) has been proven to be the most stable and useful tumor-diagnostic agent among several radiolabelled BLMs. However, the considerably long half life of 57Co causes troubles in handling and preclude its extensive uses. In our previous work, BLM was proved to form two geometrical isomers, in chelating with Co. In this paper, we compared the tumor affinity of two isomers, to make an improvement of this drug's merit. We investigated biodistribution in tumor-bearing mice and DNA binding properties by fluorescence quenching technique and DNA melting study. A comparison of the data obtained suggests that isomerism affects the tumor affinity of the drug. Both tumor accumulation in tumor-bearing mice and stability of DNA binding of type I isomer were higher than those of type II. If a certain suitable radionuclide is inserted into cold Co-BLM type I isomer, this agent will be a greatly useful tumor-imaging radiopharmaceutical.

Animals↗
PubMed1982

DNA interaction with 57Co-bleomycin.

Tumor-diagnostic 57Co-bleomycin is a mixture of two isomers: types I and II. Interaction between these and DNA was studied by fluorescence spectrometry and thermal denaturation. The fluorescence study indicated that cobalt chelation resulted in a remarkable increase in the apparent DNA-bleomycin association constant and a slight increase in bleomycin-DNA binding; a remarkable difference was observed between the two isomers. In the thermal denaturation study, the difference of DNA binding behavior was also observed. The tumor affinity of these isomers was slightly different, and type I isomer showed higher tumor affinity than type II. These results indicate that cobalt chelation to bleomycin enhances DNA-bleomycin binding and its DNA binding stability, and these mechanisms, although not fully understood, appear to underly the difference in tumor affinity of cobalt-bleomycin isomers.

Animals↗
PubMed1980

Chemical properties and tumor affinity of separated isomers of cobalt-bleomycin.

Co-57 bleomycin is a chemically stable and diagnostically useful radiopharmaceutical. Stoichiometric preparation of Co-bleomycin causes two chemically different complexes. Four kinds of chelates (A2- type I, A2-type II, B2-type I and B2-type II) are easily separated by silicagel then-layer chromatography. Circular dicroism study of these chelates indicate that two types of complexes are conformational isomers. This chemical difference is assumed to cause the difference in the biological behavior. The biodistribution study of each type of complex, using tumor-bearing mice, showed higher tumor-to-blood ratios and tumor-to muscle ratios as compared with the clinical grade Co-bleomycin mixture. But the difference between the two types was not as large as expected. The similarity in biologic bahavior suggests that the groups on the bleomycin molecule, which are concerned with chelate formation, do not take part in its binding to DNA.

Animals↗