Effect of modification of the carboxyl groups of the sialic acid binding lectin from bullfrog (Rana catesbeiana) oocyte on anti-tumor activity.
The sialic acid binding lectin from bullfrog Rana catesbeiana oocyte (cSBL) is known to have anti-tumor activity. In order to investigate the relationship between the net charge of cSBL and its anti-tumor effect, cSBL was modified with a water-soluble carbodiimide (EDC) in the presence of three kinds of nucleophiles, taurine, glycine methylester and ethylenediamine. cSBL having four carboxyl groups was partially modified (ca. 2 residues). The anti-tumor activity of modified cSBLs was in the order of ethylenediamine-modified cSBL > glycine methylester-modified cSBL > taurine modified cSBL > or = native cSBL. The results suggested that anti-tumor activity seems to increase with the increase in positive net charge, possibly enhancing the interaction of cSBL with sialoglycoprotein on the surface of tumor cells. The ribonuclease activity of ethylenediamine-modified cSBL decreased with the progress of the reaction, but the number of internalized molecules in the tumor cell increased. Thus, for antitumor activity, a higher incorporation of cSBL with reasonable RNase activity seems to be more important than total RNase activity.
Iwama
M
M
Department of Microbiology, Hoshi College of Pharmacy, Tokyo, Japan. iwama@nagaoka-ct.ac.jp
Ogawa
Y
Y
Sasaki
N
N
Nitta
K
K
Takayanagi
Y
Y
Ohgi
K
K
Tsuji
T
T
Irie
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D002942:Circular Dichroism; D005029:Ethylenediamines / Q000737:chemistry; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry; D007202:Indicators and Reagents; D037102:Lectins / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D007941:Leukemia P388 / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism*; D011506:Proteins / Q000737:chemistry; D011892:Rana catesbeiana; D012260:Ribonucleases / Q000378:metabolism; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D005029:Ethylenediamines; D007202:Indicators and Reagents; D037102:Lectins; D011506:Proteins; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C035591:glycine methyl ester; D012260:Ribonucleases; D005998:Glycine