Effect of Replacing the Aspartic Acid / Glutamic Acid Residues of Bullfrog Sialic Acid Binding Lectin with Asparagine / Glutamine and Arginine on the Inhibition of Cell Proliferation in Murine Leukemia P388 Cells
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概要
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The sialic acid binding lectin from bullfrog oocytes (cSBL) is known to have anti-tumor activity. In a previous report, to elucidate the relationship between the net charge and anti-tumor activity of cSBL, we examined the effect of chemical modifications of cSBL with a water-soluble carbodiimide in the presence of various nudeophiles. The results suggested that the anti-tumor activity and internalization into tumor cells increased with an increase in the net charge of cSBL. However, in the chemically modified cSBL, a modification site was observed on average in two of the carboxyl groups of cSBL. To confirm these previous results and to determine which modified carboxyl group contributes to the increase in anti-tumor activity, we prepared mutants with substitutions of Asn/Gln and Arg at three acidic amino acid residues of cSBL and studied their anti-tumor activity and internalization efficiency. The results showed the enhancing effect of charge on anti-tumor activity and internalization, and suggested that the replacement of D24 and E88 of cSBL with arginine is more effective than that of E97. The double mutant D24RE88R showed comparable anti-tumor activity to the ethylenediamine-modified cSBL reported previously. The mutant was well-characterized as a pure cSBL derivative suitable for studying the mechanism of the anti-tumor action of cSBL.
- 公益社団法人日本薬学会の論文
- 2002-06-01
著者
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Kobayashi H
National Food Research Institute
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Kobayashi H
National Food Res. Inst. Ibaraki Jpn
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Irie Masachika
Department of Microbiology, Hoshi College of Pharmacy
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Ohgi Kazuko
Department of Microbiology, Hoshi College of Pharmacy
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Ogawa Y
Department Of Applied Microbiology Hoshi University
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Ogawa Yuko
School Of Pharmaceutical Sciences Mukogawa Women's University
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TSUJI Tsutomu
Department of Legal Medicine, Wakayama Medical University
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Ohgi K
Department Of Applied Microbiology Faculty Of Pharmaceutical Sciences Hoshi University
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Ohgi Kazuko
Department Of Microbiology Hoshi College Of Pharmacy
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Irie M
Department Of Applied Microbiology Faculty Of Pharmaceutical Sciences Hoshi University
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Irie Masachika
Department Of Applied Microbiology Faculty Of Pharmaceutical Sciences Hoshi University
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Irie Masachika
Department Of Microbiology Hoshi College Of Pharmacy
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Kiuchi Hiroshi
Research Development Section Kibun Food Chemifa Co. Ltd.
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Hayashi K
National Food Research Institute Ministry Of Agriculture Forestry And Fisheries
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KOBAYASHI Hiroko
Department of Internal Medicine II, Fukushima Medical University School of Medicine
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ITAGAKI Tadashi
Department of Microbiology, College of Pharmacy, Nihon University
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IWAMA Masanori
Department of Applied Microbiology, Faculty of Pharmaceutical Sciences, Hoshi University
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INOKUCHI Norio
Department of Microbiology, College of Pharmacy, Nihon University
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OGAWA Yuko
Department of Microbiology, Hoshi College of Pharmacy
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Ogawa Yuko
Department Of Applied Microbiology Hoshi University
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Itagaki Tadashi
Department Of Microbiology College Of Pharmacy Nihon University
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Irie M
Hoshi Coll. Pharmacy Tokyo Jpn
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Iwama M
Department Of Microbiology Faculty Of Pharmaceutical Sciences Ohu-university
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Tsuji T
Microbiology Faculty Of Pharmaceutical Sciences Hoshi University
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Tsuji Tsutomu
Department Of Legal Medicine Wakayama Medical University
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Inokuchi N
Department Of Microbiology College Of Pharmacy Nihon University
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Kobayashi Hiroko
Department Of Gastroenterology And Rheumatology Fukushima Medical University School Of Medicine
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Ohgi Kazuko
Department Of Applied Microbiology Faculty Of Pharmaceutical Sciences Hoshi University
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Ohgi K
Department Of Microbiology Hoshi College Of Pharmacy
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Kobayashi Hiroko
Department of Cardiovascular Disease Research, Eisai Tsukuba Research Laboratories
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