Artocarpin (BioDeep_00000602710)
PANOMIX_OTCML-2023
代谢物信息卡片
2-(2,4-Dihydroxyphenyl)-5-hydroxy-7-methoxy-6-(3-methyl-1-butenyl)-3-(3-methyl-2-butenyl)-4H-1-benzopyran-4-one
化学式: C26H28O6 (436.1885788)
中文名称: 2,4,5-三羟基-7-甲氧基-6-(3-甲基-1-丁烯基)-3-(3-甲基-2-丁烯基)黄酮
谱图信息:
最多检出来源 () 0%
分子结构信息
SMILES: C1(OC)=CC2OC(C3C(O)=CC(O)=CC=3)=C(C/C=C(\C)/C)C(=O)C=2C(O)=C1C/C=C(\C)/C
InChI: InChI=1S/C26H28O6/c1-14(2)6-9-18-21(31-5)13-22-23(24(18)29)25(30)19(10-7-15(3)4)26(32-22)17-11-8-16(27)12-20(17)28/h6-8,11-13,27-29H,9-10H2,1-5H3
描述信息
A trihydroxyflavone that is flavone substituted by hydroxy groups at positions 5, 2, and 4, a methoxy group at position 7, a prenyl group at position 3 and a (1E)-3-methylbut-1-enyl group at position 6. Isolated from Artocarpus heterophyllus and Artocarpus integrifolia, it exhibits antineoplastic activity.
D007155 - Immunologic Factors > D000373 - Agglutinins > D037121 - Plant Lectins
D007155 - Immunologic Factors > D000373 - Agglutinins > D037102 - Lectins
同义名列表
数据库引用编号
8 个数据库交叉引用编号
- ChEBI: CHEBI:65439
- PubChem: 5458461
- PubChem: 44258292
- Metlin: METLIN49326
- ChEMBL: CHEMBL72617
- LipidMAPS: LMPK12110898
- CAS: 7608-44-8
- MetaboLights: MTBLC65439
分类词条
相关代谢途径
Reactome(0)
BioCyc(0)
PlantCyc(0)
代谢反应
0 个相关的代谢反应过程信息。
Reactome(0)
BioCyc(0)
WikiPathways(0)
Plant Reactome(0)
INOH(0)
PlantCyc(0)
COVID-19 Disease Map(0)
PathBank(0)
PharmGKB(0)
5 个相关的物种来源信息
- 194251 - Artocarpus altilis:
- 709040 - Artocarpus chama:
- 1867283 - Artocarpus gomezianus: 10.1055/S-2000-8656
- 3489 - Artocarpus heterophyllus:
- 3490 - Artocarpus integer: 10.1016/0031-9422(95)00135-T
在这里通过桑基图来展示出与当前的这个代谢物在我们的BioDeep知识库中具有相关联信息的其他代谢物。在这里进行关联的信息来源主要有：
- PubMed: 来源于PubMed文献库中的文献信息，我们通过自然语言数据挖掘得到的在同一篇文献中被同时提及的相关代谢物列表，这个列表按照代谢物同时出现的文献数量降序排序，取前10个代谢物作为相关研究中关联性很高的代谢物集合展示在桑基图中。
- NCBI Taxonomy: 通过文献数据挖掘，得到的代谢物物种来源信息关联。这个关联信息同样按照出现的次数降序排序，取前10个代谢物作为高关联度的代谢物集合展示在桑吉图上。
- Chemical Taxonomy: 在物质分类上处于同一个分类集合中的其他代谢物
- Chemical Reaction: 在化学反应过程中，存在为当前代谢物相关联的生化反应过程中的反应底物或者反应产物的关联代谢物信息。
点击图上的相关代谢物的名称，可以跳转到相关代谢物的信息页面。
文献列表
- Murugan Thulasi Meenu, Grace Kaul, Abdul Akhir, Manjulika Shukla, Kokkuvayil Vasu Radhakrishnan, Sidharth Chopra. Developing the Natural Prenylflavone Artocarpin from Artocarpus hirsutus as a Potential Lead Targeting Pathogenic, Multidrug-Resistant Staphylococcus aureus, Persisters and Biofilms with No Detectable Resistance.
Journal of natural products.
2022 10; 85(10):2413-2423. doi:
10.1021/acs.jnatprod.2c00621. [PMID: 36222797] - Qirou Wang, Ruilin Li, Nannan Li, Yanan Jia, Yajie Wang, Yue Chen, Pharkphoom Panichayupakaranant, Haixia Chen. The antioxidant activities, inhibitory effects, kinetics, and mechanisms of artocarpin and α-mangostin on α-glucosidase and α-amylase.
International journal of biological macromolecules.
2022 Jul; 213(?):880-891. doi:
10.1016/j.ijbiomac.2022.06.017. [PMID: 35688278] - R R Bazmi, P Panichayupakaranant. Synergistic interactions between artocarpin-rich extract, lawsone methyl ether and ampicillin on anti-MRSA and their antibiofilm formation.
Letters in applied microbiology.
2022 May; 74(5):777-786. doi:
10.1111/lam.13662. [PMID: 35100449] - Abdi Wira Septama, Eldiza Puji Rahmi, Lucia Dwi Antika, Rizna Triana Dewi, Amit Jaisi. A synergy interaction of artocarpin and tetracycline against Pseudomonas aeruginosa and its mechanism of action on membrane permeability.
Zeitschrift fur Naturforschung. C, Journal of biosciences.
2022 Jan; 77(1-2):57-63. doi:
10.1515/znc-2021-0076. [PMID: 34105319] - Sukanya Dej-Adisai, Kedsaraporn Parndaeng, Chatchai Wattanapiromsakul, Jae Sung Hwang. Three New Isoprenylated Flavones from Artocarpus chama Stem and Their Bioactivities.
Molecules (Basel, Switzerland).
2021 Dec; 27(1):. doi:
10.3390/molecules27010003. [PMID: 35011235] - Yana Sharapova, Vytas Švedas, Dmitry Suplatov. Catalytic and lectin domains in neuraminidase A from Streptococcus pneumoniae are capable of an intermolecular assembly: Implications for biofilm formation.
The FEBS journal.
2021 05; 288(10):3217-3230. doi:
10.1111/febs.15610. [PMID: 33108702] - Isaac J Morrison, Jianan Zhang, Jingwen Lin, JeAnn E Murray, Roy Porter, Moses K Langat, Nicholas J Sadgrove, James Barker, Guodong Zhang, Rupika Delgoda. Potential chemopreventive, anticancer and anti-inflammatory properties of a refined artocarpin-rich wood extract of Artocarpus heterophyllus Lam.
Scientific reports.
2021 03; 11(1):6854. doi:
10.1038/s41598-021-86040-5. [PMID: 33767225] - Kunlathida Luangpraditkun, Marion Tissot, Anupong Joompang, Pensri Charoensit, François Grandmottet, Jarupa Viyoch, Céline Viennet. Prevention by the Natural Artocarpin of Morphological and Biochemical Alterations on UVB-Induced HaCaT Cells.
Oxidative medicine and cellular longevity.
2021; 2021(?):5067957. doi:
10.1155/2021/5067957. [PMID: 34306307] - Hua Jiang, Xiangcai Meng, Xianbao Shi, Jingming Yang. Interspecies metabolic diversity of artocarpin in vitro mammalian liver microsomes.
Bioscience, biotechnology, and biochemistry.
2020 Apr; 84(4):661-669. doi:
10.1080/09168451.2019.1701405. [PMID: 31829112] - Kunlathida Luangpraditkun, Pensri Charoensit, François Grandmottet, Céline Viennet, Jarupa Viyoch. Photoprotective Potential of the Natural Artocarpin against In Vitro UVB-Induced Apoptosis.
Oxidative medicine and cellular longevity.
2020; 2020(?):1042451. doi:
10.1155/2020/1042451. [PMID: 33014267] - Chiang-Wen Lee, Miao-Ching Chi, Tsung-Ming Chang, Ju-Fang Liu. Artocarpin induces cell apoptosis in human osteosarcoma cells through endoplasmic reticulum stress and reactive oxygen species.
Journal of cellular physiology.
2019 08; 234(8):13157-13168. doi:
10.1002/jcp.27986. [PMID: 30549031] - Wei Qu, Xuezheng Liu. Identification of cytochrome P450 isoforms involved in the metabolism of artocarpin and assessment of its drug-drug interaction.
Biomedical chromatography : BMC.
2018 Apr; 32(4):. doi:
10.1002/bmc.4149. [PMID: 29166542] - Mai T T Nguyen, Tho H Le, Hai X Nguyen, Phu H Dang, Truong N V Do, Manabu Abe, Ryukichi Takagi, Nhan T Nguyen. Artocarmins G-M, Prenylated 4-Chromenones from the Stems of Artocarpus rigida and Their Tyrosinase Inhibitory Activities.
Journal of natural products.
2017 12; 80(12):3172-3178. doi:
10.1021/acs.jnatprod.7b00453. [PMID: 29227656] - Chung-Ju Yeh, Chin-Chuan Chen, Yann-Lii Leu, Ming-Wei Lin, Mei-Miao Chiu, Shu-Huei Wang. The effects of artocarpin on wound healing: in vitro and in vivo studies.
Scientific reports.
2017 Nov; 7(1):15599. doi:
10.1038/s41598-017-15876-7. [PMID: 29142215] - Narisara Tiraravesit, Philippe Humbert, Sophie Robin, Marion Tissot, Céline Viennet, Jarupa Viyoch. Artocarpin-enriched (Artocarpus altilis) Heartwood Extract Provides Protection Against UVB-induced Mechanical Damage in Dermal Fibroblasts.
Photochemistry and photobiology.
2017 10; 93(5):1232-1239. doi:
10.1111/php.12788. [PMID: 28477344] - Jutatip Kwankaew, Preeyawass Phimnuan, Sombat Wanauppathamkul, Jarupa Viyoch. Formulation of chitosan patch incorporating Artocarpus altilis heartwood extract for improving hyperpigmentation.
Journal of cosmetic science.
2017 Jul; 68(4):257-269. doi:
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Journal of agricultural and food chemistry.
2017 May; 65(17):3474-3480. doi:
10.1021/acs.jafc.7b00278. [PMID: 28391699] - Siti Awanis Abdullah, Shajarahtunnur Jamil, Norazah Basar, Siti Mariam Abdul Lathiff, Norzafneza Mohd Arriffin. Flavonoids from the leaves and heartwoods of Artocarpus lowii King and their bioactivities.
Natural product research.
2017 May; 31(10):1113-1120. doi:
10.1080/14786419.2016.1222387. [PMID: 27564208] - Ming-Horng Tsai, Ju-Fang Liu, Yao-Chang Chiang, Stephen Chu-Sung Hu, Lee-Fen Hsu, Yu-Ching Lin, Zih-Chan Lin, Hui-Chun Lee, Mei-Chuan Chen, Chieh-Liang Huang, Chiang-Wen Lee. Artocarpin, an isoprenyl flavonoid, induces p53-dependent or independent apoptosis via ROS-mediated MAPKs and Akt activation in non-small cell lung cancer cells.
Oncotarget.
2017 Apr; 8(17):28342-28358. doi:
10.18632/oncotarget.16058. [PMID: 28423703] - Cheng-Wei Tzeng, Wen-Sheng Tzeng, Liang-Tzung Lin, Chiang-Wen Lee, Feng-Lin Yen, Chun-Ching Lin. Enhanced autophagic activity of artocarpin in human hepatocellular carcinoma cells through improving its solubility by a nanoparticle system.
Phytomedicine : international journal of phytotherapy and phytopharmacology.
2016 May; 23(5):528-40. doi:
10.1016/j.phymed.2016.02.010. [PMID: 27064012] - Abdi Wira Septama, Pharkphoom Panichayupakaranant. Synergistic effect of artocarpin on antibacterial activity of some antibiotics against methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli.
Pharmaceutical biology.
2016; 54(4):686-91. doi:
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International journal of medical microbiology : IJMM.
2015 May; 305(3):289-97. doi:
10.1016/j.ijmm.2014.12.004. [PMID: 25592264] - Sukanya Dej-Adisai, Imron Meechai, Jindaporn Puripattanavong, Sopa Kummee. Antityrosinase and antimicrobial activities from Thai medicinal plants.
Archives of pharmacal research.
2014 Apr; 37(4):473-83. doi:
10.1007/s12272-013-0198-z. [PMID: 23835832] - Cheng-Wei Tzeng, Feng-Lin Yen, Liang-Tzung Lin, Chiang-Wen Lee, Ming-Hong Yen, Wen-Sheng Tzeng, Chun-Ching Lin. Antihepatoma activity of Artocarpus communis is higher in fractions with high artocarpin content.
TheScientificWorldJournal.
2014; 2014(?):978525. doi:
10.1155/2014/978525. [PMID: 25133268] - Chiang-Wen Lee, Horng-Huey Ko, Chun-Ching Lin, Chee-Yin Chai, Wan-Tzu Chen, Feng-Lin Yen. Artocarpin attenuates ultraviolet B-induced skin damage in hairless mice by antioxidant and anti-inflammatory effect.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.
2013 Oct; 60(?):123-9. doi:
10.1016/j.fct.2013.07.029. [PMID: 23871788] - David Giménez-Romero, Paulo R Bueno, Naira C Pesquero, Isidro S Monzó, Rosa Puchades, Ángel Maquieira. Elucidation of carbohydrate molecular interaction mechanism of recombinant and native ArtinM.
The journal of physical chemistry. B.
2013 Jul; 117(28):8360-9. doi:
10.1021/jp403087p. [PMID: 23799777] - Xin Qiao, Ting Zhao, Meng Wang, Chun Lei, Aijun Hou. [Flavonoids from Artocarpus hypargyreus].
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica.
2011 Nov; 36(21):2975-9. doi:
10.4268/cjcmm20112117. [PMID: 22308687] - Enos Tangke Arung, Kuniyoshi Shimizu, Ryuichiro Kondo. Artocarpus plants as a potential source of skin whitening agents.
Natural product communications.
2011 Sep; 6(9):1397-402. doi:
. [PMID: 21941923] - Supasiri Buranajaree, Piyaporn Donsing, Rattima Jeenapongsa, Jarupa Viyoch. Depigmenting action of a nanoemulsion containing heartwood extract of Artocarpus incisus on UVB-induced hyperpigmentation in C57BL/6 mice.
Journal of cosmetic science.
2011 Jan; 62(1):1-14. doi:
". [PMID: 21443841] - Carla Oliveira, Ana Nicolau, José A Teixeira, Lucília Domingues. Cytotoxic effects of native and recombinant frutalin, a plant galactose-binding lectin, on HeLa cervical cancer cells.
Journal of biomedicine & biotechnology.
2011; 2011(?):568932. doi:
10.1155/2011/568932. [PMID: 22131813] - Enzo A Palombo. Traditional Medicinal Plant Extracts and Natural Products with Activity against Oral Bacteria: Potential Application in the Prevention and Treatment of Oral Diseases.
Evidence-based complementary and alternative medicine : eCAM.
2011; 2011(?):680354. doi:
10.1093/ecam/nep067. [PMID: 19596745] - Enos Tangke Arung, Britanto Dani Wicaksono, Yohana Ayupriyanti Handoko, Irawan Wijaya Kusuma, Kuniyoshi Shimizu, Dina Yulia, Ferry Sandra. Cytotoxic effect of artocarpin on T47D cells.
Journal of natural medicines.
2010 Oct; 64(4):423-9. doi:
10.1007/s11418-010-0425-6. [PMID: 20544395] - Shireen Shaharina Shamaun, Mawardi Rahmani, Najihah Mohd Hashim, Hazar Bebe Mohd Ismail, Mohd Aspollah Sukari, Gwendoline Ee Cheng Lian, Rusea Go. Prenylated flavones from Artocarpus altilis.
Journal of natural medicines.
2010 Oct; 64(4):478-81. doi:
10.1007/s11418-010-0427-4. [PMID: 20526745] - Ashwini S Hinge, Lalita S Limaye, Avadhesha Surolia, Vaijayanti P Kale. In vitro protection of umbilical cord blood-derived primitive hematopoietic stem progenitor cell pool by mannose-specific lectins via antioxidant mechanisms.
Transfusion.
2010 Aug; 50(8):1815-26. doi:
10.1111/j.1537-2995.2010.02647.x. [PMID: 20412533] - Enos Tangke Arung, Keisuke Yoshikawa, Kuniyoshi Shimizu, Ryuichiro Kondo. Isoprenoid-substituted flavonoids from wood of Artocarpus heterophyllus on B16 melanoma cells: cytotoxicity and structural criteria.
Fitoterapia.
2010 Mar; 81(2):120-3. doi:
10.1016/j.fitote.2009.08.001. [PMID: 19686821] - Yan-long Yang, Ai-jun Hou, Hui-qing Zhang, Hong Shen, Qiu-shuang Li, Cong-cong Zhang, Guo-fu Zhu. [Effects of cycloartocarpin A and artocarpin extracted from Fructus Artocarpin Heterophylli on apoptosis of SMMC-7721 and SGC-7901 cells].
Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine.
2010 Jan; 8(1):61-6. doi:
10.3736/jcim20100112. [PMID: 20082761] - Henri Debray, Bernadette Coddeville, Liezelotte R Bomfim, Márcio V Ramos. A simple micro-method for determining precise oligosaccharidic specificity of mannose-binding lectins.
Glycobiology.
2009 Dec; 19(12):1417-26. doi:
10.1093/glycob/cwp091. [PMID: 19542523] - Hervé Benoist, Raphaël Culerrier, Guillaume Poiroux, Bruno Ségui, Alain Jauneau, Els J M Van Damme, Willy J Peumans, Annick Barre, Pierre Rougé. Two structurally identical mannose-specific jacalin-related lectins display different effects on human T lymphocyte activation and cell death.
Journal of leukocyte biology.
2009 Jul; 86(1):103-14. doi:
10.1189/jlb.0708434. [PMID: 19401384] - Fernando Chahud, Leandra N Z Ramalho, Fernando S Ramalho, Antonio Haddad, Maria C Roque-Barreira. The lectin KM+ induces corneal epithelial wound healing in rabbits.
International journal of experimental pathology.
2009 Apr; 90(2):166-73. doi:
10.1111/j.1365-2613.2008.00626.x. [PMID: 19335555] - Karina Alves Toledo, Carolina Scwartz, Aline Ferreira Oliveira, Marina Cavalcanti Albuquerque Veiga Conrado, Emerson Soares Bernardes, Luiz Cláudio Fernandes, Maria Cristina Roque-Barreira, Gabriela Pereira-da-Silva, Andréa Novais Moreno. Neutrophil activation induced by ArtinM: release of inflammatory mediators and enhancement of effector functions.
Immunology letters.
2009 Mar; 123(1):14-20. doi:
10.1016/j.imlet.2009.01.009. [PMID: 19428547] - Zong-Ping Zheng, Ka-Wing Cheng, James Tsz-Kin To, Haitao Li, Mingfu Wang. Isolation of tyrosinase inhibitors from Artocarpus heterophyllus and use of its extract as antibrowning agent.
Molecular nutrition & food research.
2008 Dec; 52(12):1530-8. doi:
10.1002/mnfr.200700481. [PMID: 18683821] - Gabriela Pereira-da-Silva, Maria Cristina Roque-Barreira, Els J M Van Damme. Artin M: a rational substitution for the names artocarpin and KM+.
Immunology letters.
2008 Aug; 119(1-2):114-5. doi:
10.1016/j.imlet.2008.06.002. [PMID: 18602950] - Sachiko Nakamura-Tsuruta, Noboru Uchiyama, Willy J Peumans, Els J M Van Damme, Kiichiro Totani, Yukishige Ito, Jun Hirabayashi. Analysis of the sugar-binding specificity of mannose-binding-type Jacalin-related lectins by frontal affinity chromatography--an approach to functional classification.
The FEBS journal.
2008 Mar; 275(6):1227-39. doi:
10.1111/j.1742-4658.2008.06282.x. [PMID: 18266762] - Piyaporn Donsing, Nanteetip Limpeanchob, Jarupa Viyoch. Evaluation of the effect of Thai breadfruit's heartwood extract on melanogenesis-inhibitory and antioxidation activities.
Journal of cosmetic science.
2008 Jan; 59(1):41-58. doi:
. [PMID: 18350234] - Tasana Pitaksuteepong, Atawit Somsiri, Neti Waranuch. Targeted transfollicular delivery of artocarpin extract from Artocarpus incisus by means of microparticles.
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.
2007 Nov; 67(3):639-45. doi:
10.1016/j.ejpb.2007.03.019. [PMID: 17493791] - Enos Tangke Arung, Kuniyoshi Shimizu, Ryuichiro Kondo. Inhibitory effect of isoprenoid-substituted flavonoids isolated from Artocarpus heterophyllus on melanin biosynthesis.
Planta medica.
2006 Jul; 72(9):847-50. doi:
10.1055/s-2006-931606. [PMID: 16732541] - Ah-Reum Han, You-Jin Kang, Tri Windono, Sang Kook Lee, Eun-Kyoung Seo. Prenylated flavonoids from the heartwood of Artocarpus communis with inhibitory activity on lipopolysaccharide-induced nitric oxide production.
Journal of natural products.
2006 Apr; 69(4):719-21. doi:
10.1021/np0600346. [PMID: 16643064] - Gabriela Pereira-da-Silva, Andréa N Moreno, Fabiana Marques, Constance Oliver, Maria Célia Jamur, Ademilson Panunto-Castelo, Maria Cristina Roque-Barreira. Neutrophil activation induced by the lectin KM+ involves binding to CXCR2.
Biochimica et biophysica acta.
2006 Jan; 1760(1):86-94. doi:
10.1016/j.bbagen.2005.09.011. [PMID: 16260092] - Luciane Ganiko, Antônio R Martins, Edna Freymüller, Renato A Mortara, Maria-Cristina Roque-Barreira. Lectin KM+-induced neutrophil haptotaxis involves binding to laminin.
Biochimica et biophysica acta.
2005 Jan; 1721(1-3):152-63. doi:
10.1016/j.bbagen.2004.10.012. [PMID: 15652190] - Muthia Rajendran, Paramasivam Manisankar, Rathinasamy Gandhidasan, Ramachandran Murugesan. Free radicals scavenging efficiency of a few naturally occurring flavonoids: a comparative study.
Journal of agricultural and food chemistry.
2004 Dec; 52(24):7389-94. doi:
10.1021/jf0400718. [PMID: 15563224] - Annick Barre, Willy J Peumans, Michel Rossignol, Gisèle Borderies, Raphaël Culerrier, Els J M Van Damme, Pierre Rougé. Artocarpin is a polyspecific jacalin-related lectin with a monosaccharide preference for mannose.
Biochimie.
2004 Sep; 86(9-10):685-91. doi:
10.1016/j.biochi.2004.09.001. [PMID: 15556279] - A Arockia Jeyaprakash, Anand Srivastav, A Surolia, M Vijayan. Structural basis for the carbohydrate specificities of artocarpin: variation in the length of a loop as a strategy for generating ligand specificity.
Journal of molecular biology.
2004 May; 338(4):757-70. doi:
10.1016/j.jmb.2004.03.040. [PMID: 15099743] - Yong-Hong Wang, Ai-Jun Hou, Lei Chen, Dao-Feng Chen, Han-Dong Sun, Qin-Shi Zhao, Kenneth F Bastow, Yuka Nakanish, Xi-Hong Wang, Kuo-Hsiung Lee. New isoprenylated flavones, artochamins A--E, and cytotoxic principles from Artocarpus chama.
Journal of natural products.
2004 May; 67(5):757-61. doi:
10.1021/np030467y. [PMID: 15165133] - J V Pratap, A Arockia Jeyaprakash, P Geetha Rani, K Sekar, A Surolia, M Vijayan. Crystal structures of artocarpin, a Moraceae lectin with mannose specificity, and its complex with methyl-alpha-D-mannose: implications to the generation of carbohydrate specificity.
Journal of molecular biology.
2002 Mar; 317(2):237-47. doi:
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Planta medica.
2002 Jan; 68(1):79-81. doi:
10.1055/s-2002-20057. [PMID: 11842337] - P G Rani, K Bachhawat, G B Reddy, S Oscarson, A Surolia. Isothermal titration calorimetric studies on the binding of deoxytrimannoside derivatives with artocarpin: implications for a deep-seated combining site in lectins.
Biochemistry.
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The Journal of biological chemistry.
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The Journal of biological chemistry.
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Journal of immunological methods.
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