相思子毒素的分子特点及其在临床中的应用前景
李丽琴，郑晓军，史瑞雪，陈乐贵，林福生
[摘要] 相思子毒素是从豆科植物(Abrus Precatorius L.)种子中分离的一种细胞毒性蛋白。它由A，B两条链组成，由一个二硫键相联，B链具有半乳糖凝集活性，可与细胞膜上受体结合，帮助A链进入细胞内，A链进入细胞催化失活60S核糖体亚基，从而使细胞蛋白合成被抑制。本文综述了有关相思子毒素的分子结构特点，毒性机制和在临床中的应用前景。
[关键词] 相思子毒素; 结构特点; 免疫毒素 ; 临床应用
MOLECULAR CHARACTERISTICS AND CLINICAL
APPLICATION PROSPECT OF ABRIN
Li liqin , Zheng xiaojun ,Shi ruixue, Chen legui,Lin fusheng
, 百拇医药
( Pharmaceutical Chemistry Institute of Beijing BeiJing 102205)
[Abstract] Abrin is one of the potent toxins isolated from the beans of plant Abrus precatorius.The toxic protein consists of two disulfide-bonded subunits,the A and B chains.The B chain is a galactose-specific lectin that facilitates the binding of abrin to the cell membrane that precedes endocytosis.After entering the cells,the A chain catalytically inactivates 60S ribosomal subunits by removing adenine position 4324 of 28S r–RNA，and thereby inhibits protein biosynthesis. This literature on abrin has been reviewed with respect to：(i)the abrin structural characteristics, (ii) action mechanism of causing poison of abrin,(iii) application prospect in clinical of abrin.
, http://www.100md.com
[Key Words] abrin；structural characteristics；immunotoxin；clinical application
[参考文献]
[1] Chen YL,Lin JY. The complete primary structure of abrin-a A-chain[J]. J Chin Biochem
Soc,1994,23:1-14.
[2] Chen YL,Chow LP,Tsugita A,et al. The complete primary structure of abrin-a B
chain[J]. FEBS, 1992,309(2):115-118.
, http://www.100md.com
[3] Kimura M,Sumizawa T, Funatsu G,et al. The complete amino acid sequences of the B-chains
of abrin-a and abrin-b, Toxic proteins from the seeds of Abrus precatorius[J]. Biosci Biotechnd Biochem,1993,57(1):166-169.
[4] Evensen G,Mathiesen A,Sundan A,et al.Direct molecular cloning and Expression of two
distinct abrin A-chain[J]. J Biol Chem, 1991,266:6848-6852.
, 百拇医药
[5] Wood CA,Lord JM,Wawrzynczak EJ,et al.Preproabrin: genomic cloning, characterisation and the expression of the A-chain in Escherichia coli[J]. Eur J Biochem, 1991,198:723-732.
[6] Hung CH, Lee MC, LEE TC,et al. Primary structure of three distinct isoabrins determined
by cDNA sequencing:conservation and significance[J].J Mol Biol, 1993,229(1):263-267.
[7] Hedge R, Podder SK. A- and B-Subunit variant distribution in the holoprotein variants
, 百拇医药
of protein toxin abrin: Variants of abrins I and III have constant toxic A subunits and variant lectin B subunits[J].Arch Biochem Biophys,1997,344(1):75-84.
[8] Hung CH,Lee MC,Chen JK,et al.Cloning and expression of three abrin A-chains and their
mutants derived by site-specific mutagenesis in Escherichia coli[J]. Eur J Biochem, 1994,219:83-87.
[9] Tahirov TH,Lu TH,Liaw YC,et al. Crystal structure of abrin-a at 2.14A[J]. J Mol Biol,1995,250:354-367.
, http://www.100md.com
[10] Tahirov TH,Lu TH,Liaw YC,et al. Crystal structure of abrin-a at 2.1A[J]. J Mol Biol,1995,250:346-354.
[11] Tahirov TH,Lu TH,Liaw YC,et al. A new Crystal form of abrin-a from the seeds of Abrus precatorius[J]. J Mol Biol,1994,235:1152-1153.
[12] Lin SH,Chow LP,Chen YL,et al. Probing the domain structure of abrin-a by tryptic
digestion[J].Eur J Biochem,1996,240:564-569.
, 百拇医药
[13] Tung TC. Orally administrable anti-metastatic lectin compositions and methods[P].
US patent:5053386,1991-10-01.
[14] Wawrzynczak EJ,Zangemeister-Wittke U,Waibel R,et al. Molecular and biological
properties of an abrin A chain immunotoxin designed for therapy of human small cell lung cancer[J].Br J Cancer,1992,66:361-366.
[15] Tsai LC,Chen YL,Lee C,et al. Growth suppression of human aolorectal carcinoma in nude
, 百拇医药
mice by monoclonal antibody C27-abrin A chain conjugate[J].Dis Colon Rectum,1995,38(10):1067-1074.
[16] Nett TM, Glode LM. GNRH analogs for destroying gonadotrophs[P]. US patent:5378688,1995-06-03.
[17] Frankel A,Fu T,Burbage C,et al. IL-2 Fused to lectin-deficient ricin A is toxic to
human leukemia cells expressing the IL-2 recepor[J].Leukemia,1997,(11):22-30.
, 百拇医药 [18] Frankel AE,Laver JH,Willingham M,et al. Therapy of patients with T-cell lymphomas and
leukemias using an anti-CD7 monoclonal antibody-ricin A chain Immunotoxin[J].Leukemia and lymphoma,1997,26:287-298.
[19] UYRP.New biotin derivatives are biotinidase-resistant useful as conjugates for targeting of diagnostic and therapeutic agents[P].US Patent:5807879,1998-04-04.
[20] AGEN.New cell growth inhibitor-comprises abrin a[P].JP patent:11080019,1999-02-02., 百拇医药
[摘要] 相思子毒素是从豆科植物(Abrus Precatorius L.)种子中分离的一种细胞毒性蛋白。它由A，B两条链组成，由一个二硫键相联，B链具有半乳糖凝集活性，可与细胞膜上受体结合，帮助A链进入细胞内，A链进入细胞催化失活60S核糖体亚基，从而使细胞蛋白合成被抑制。本文综述了有关相思子毒素的分子结构特点，毒性机制和在临床中的应用前景。
[关键词] 相思子毒素; 结构特点; 免疫毒素 ; 临床应用
MOLECULAR CHARACTERISTICS AND CLINICAL
APPLICATION PROSPECT OF ABRIN
Li liqin , Zheng xiaojun ,Shi ruixue, Chen legui,Lin fusheng
, 百拇医药
( Pharmaceutical Chemistry Institute of Beijing BeiJing 102205)
[Abstract] Abrin is one of the potent toxins isolated from the beans of plant Abrus precatorius.The toxic protein consists of two disulfide-bonded subunits,the A and B chains.The B chain is a galactose-specific lectin that facilitates the binding of abrin to the cell membrane that precedes endocytosis.After entering the cells,the A chain catalytically inactivates 60S ribosomal subunits by removing adenine position 4324 of 28S r–RNA，and thereby inhibits protein biosynthesis. This literature on abrin has been reviewed with respect to：(i)the abrin structural characteristics, (ii) action mechanism of causing poison of abrin,(iii) application prospect in clinical of abrin.
, http://www.100md.com
[Key Words] abrin；structural characteristics；immunotoxin；clinical application
[参考文献]
[1] Chen YL,Lin JY. The complete primary structure of abrin-a A-chain[J]. J Chin Biochem
Soc,1994,23:1-14.
[2] Chen YL,Chow LP,Tsugita A,et al. The complete primary structure of abrin-a B
chain[J]. FEBS, 1992,309(2):115-118.
, http://www.100md.com
[3] Kimura M,Sumizawa T, Funatsu G,et al. The complete amino acid sequences of the B-chains
of abrin-a and abrin-b, Toxic proteins from the seeds of Abrus precatorius[J]. Biosci Biotechnd Biochem,1993,57(1):166-169.
[4] Evensen G,Mathiesen A,Sundan A,et al.Direct molecular cloning and Expression of two
distinct abrin A-chain[J]. J Biol Chem, 1991,266:6848-6852.
, 百拇医药
[5] Wood CA,Lord JM,Wawrzynczak EJ,et al.Preproabrin: genomic cloning, characterisation and the expression of the A-chain in Escherichia coli[J]. Eur J Biochem, 1991,198:723-732.
[6] Hung CH, Lee MC, LEE TC,et al. Primary structure of three distinct isoabrins determined
by cDNA sequencing:conservation and significance[J].J Mol Biol, 1993,229(1):263-267.
[7] Hedge R, Podder SK. A- and B-Subunit variant distribution in the holoprotein variants
, 百拇医药
of protein toxin abrin: Variants of abrins I and III have constant toxic A subunits and variant lectin B subunits[J].Arch Biochem Biophys,1997,344(1):75-84.
[8] Hung CH,Lee MC,Chen JK,et al.Cloning and expression of three abrin A-chains and their
mutants derived by site-specific mutagenesis in Escherichia coli[J]. Eur J Biochem, 1994,219:83-87.
[9] Tahirov TH,Lu TH,Liaw YC,et al. Crystal structure of abrin-a at 2.14A[J]. J Mol Biol,1995,250:354-367.
, http://www.100md.com
[10] Tahirov TH,Lu TH,Liaw YC,et al. Crystal structure of abrin-a at 2.1A[J]. J Mol Biol,1995,250:346-354.
[11] Tahirov TH,Lu TH,Liaw YC,et al. A new Crystal form of abrin-a from the seeds of Abrus precatorius[J]. J Mol Biol,1994,235:1152-1153.
[12] Lin SH,Chow LP,Chen YL,et al. Probing the domain structure of abrin-a by tryptic
digestion[J].Eur J Biochem,1996,240:564-569.
, 百拇医药
[13] Tung TC. Orally administrable anti-metastatic lectin compositions and methods[P].
US patent:5053386,1991-10-01.
[14] Wawrzynczak EJ,Zangemeister-Wittke U,Waibel R,et al. Molecular and biological
properties of an abrin A chain immunotoxin designed for therapy of human small cell lung cancer[J].Br J Cancer,1992,66:361-366.
[15] Tsai LC,Chen YL,Lee C,et al. Growth suppression of human aolorectal carcinoma in nude
, 百拇医药
mice by monoclonal antibody C27-abrin A chain conjugate[J].Dis Colon Rectum,1995,38(10):1067-1074.
[16] Nett TM, Glode LM. GNRH analogs for destroying gonadotrophs[P]. US patent:5378688,1995-06-03.
[17] Frankel A,Fu T,Burbage C,et al. IL-2 Fused to lectin-deficient ricin A is toxic to
human leukemia cells expressing the IL-2 recepor[J].Leukemia,1997,(11):22-30.
, 百拇医药 [18] Frankel AE,Laver JH,Willingham M,et al. Therapy of patients with T-cell lymphomas and
leukemias using an anti-CD7 monoclonal antibody-ricin A chain Immunotoxin[J].Leukemia and lymphoma,1997,26:287-298.
[19] UYRP.New biotin derivatives are biotinidase-resistant useful as conjugates for targeting of diagnostic and therapeutic agents[P].US Patent:5807879,1998-04-04.
[20] AGEN.New cell growth inhibitor-comprises abrin a[P].JP patent:11080019,1999-02-02., 百拇医药