Concanavalin A as a carrier of daunomycin

Kitao, Takeshi; Hattori, Kenichi

doi:10.1038/265081a0

Cited by 65 publications

(17 citation statements)

References 2 publications

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“…PNA, if bound to a drug, may direct and concentrate the drug on this pathologic subpopulation. The use of daunomycin bound to concanavalin A has been demonstrated in a mouse model system (17). The advantage of PNA over other lectins is that it does not interact significantly with human erythrocytes (5) or with normal peripheral blood lymphocytes.…”

Section: Methodsmentioning

confidence: 99%

Interaction of peanut agglutinin with normal human lymphocytes and with leukemic cells.

Reisner¹,

Biniaminov²,

Rosenthal³

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

118

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The interaction of peanut agglutinin (PNA) with human thymocytes, peripheral blood Imphocytes, and peripheral blood cells of various types of leuiemia was investigated by using fluorescein isothiocyanate-conjugated PNA. The majority of human thymocytes (60-80%) bind the lectin.The major subpopulation of thymocytes that is PNA-positive was separated from the PNA-negative cells by differential agglutination with the lectin. The two thymocyte subpopulations were tested in the mixed lymphocyte reaction and with the phytohemagglutinin of Phaseolus vulgaris. The poor response of the PNA-positive thymocytes to these stimuli indicates that these thymocytes are functionally immature. The fluorescein isothiocyanate-PNA-binding test with peripheral blood lymphocytes of leukemic patients revealed that in most acute leukemias the PNA receptor is exposed on the blastic cells, whereas in most cases of chronic leukemia the peripheral blood lymphocytes are PNA-negative. The validity of PNA as a marker of immature blood cells and its potential clinical application are discussed.Classification of the various leukemias according to the cellular origin of their pathologic cells is of diagnostic and therapeutic importance. However, such a classification is hampered by the scarcity of cell markers that can be attributed to lymphoid or myeloid subpopulations at specific stages of their differentiation (1). It has recently been shown that peanut agglutinin (PNA) binds exclusively to undifferentiated murine lymphocytes such as immature hydrocortisone-sensitive murine thymocytes (2), fetal liver lymphocytes (3), and bone marrow and spleen stem cells (4). On mature lymphocytes the lectin receptor is masked by sialic acid and can be exposed upon treatment of the cells with neuraminidase.In the present study we have investigated the interaction of PNA with human thymocytes, peripheral blood lymphocytes, and various types of leukemic blast cells. The validity of PNA as a marker of immature human blood cells and its potential for clinical application are discussed. MATERIALS AND METHODSPNA was purified by affinity chromatography on a column of Sepharose-N-(e-aminocaproyl)-fl-D-galactopyranosylamine (5). Fluorescein isothiocyanate (FITC) was conjugated with PNA as described (6), and the conjugated lectin was repurified by affinity chromatography. 125I-labeled PNA (125I-PNA) was prepared as described (2), and the iodinated lectin was purified on a Sephadex G-150 column followed by affinity chromatography. Phytohemagglutinin (PHA) was obtained from Wellcome-Burroughs. [methyl-3H]Thymidine (5 Ci/mmol; 1 Ci = 3.7 X 10l°becquerels) was obtained from the Nuclear Research Center, Negev, Israel. Neuraminidase of Vibrio cholera was obtained from Behringwerke, Marburg, Germany; 1 unit is defined as the amount of enzyme that liberates 1 ,ug of N-acetylneuraminic acid from a1-glycoprotein within 15 min at pH 5.5 and 370C.Cell Preparations. Normal peripheral blood lymphocytes were purified from heparinized peripheral blood by centrifugation over Fic...

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Section: Methodsmentioning

confidence: 99%

Interaction of peanut agglutinin with normal human lymphocytes and with leukemic cells.

Reisner¹,

Biniaminov²,

Rosenthal³

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

118

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“…In view of the known ability of certain lectins to preferentially bind tumor cells [11], it appeared that lectins could be used as specific targeting agents for porphyrin photosensitizers in PDT. Previous studies reporting the preparation and evaluation of the efficacy of some lectindrug conjugates on tumor cells and animal models support the above idea [12][13][14]. Therefore, we initiated a long-term Correspondence to M. J. Swamy, School of Chemistry, University of Hyderabad, Hyderabad 500 046, India.…”

mentioning

confidence: 90%

Thermodynamic analysis of porphyrin binding to Momordica charantia (bitter gourd) lectin

Sultan

Maiya²,

Swamy

2004

European Journal of Biochemistry

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Owing to the use of porphyrins in photodynamic therapy for the treatment of malignant tumors, and the preferential interaction of lectins with tumor cells, studies on lectinporphyrin interaction are of significant interest. In this study, the interaction of several free-base and metalloporphyrins with Momordica charantia (bitter gourd) lectin (MCL) was investigated by absorption spectroscopy. Difference absorption spectra revealed that significant changes occur in the Soret band region of the porphyrins on binding to MCL. These changes were monitored to obtain association constants (K a ) and stoichiometry of binding. The tetrameric MCL binds four porphyrin molecules, and the stoichiometry was unaffected by the presence of the specific sugar, lactose. In addition, the agglutination activity of MCL was unaffected by the presence of the porphyrins used in this study, clearly indicating that porphyrin and carbohydrate ligands bind at different sites. Both cationic and anionic porphyrins bind to the lectin with comparable affinity (K a ¼ ). The thermodynamic parameters associated with the interaction of several porphyrins, obtained from the temperature dependence of the K a values, were found to be in the range: DH°¼ )98.1 to )54.4 kJAEmol )1 and DS°¼ )243.9 to )90.8 JAEmol . These results indicate that porphyrin binding to MCL is governed by enthalpic forces and that the contribution from binding entropy is negative. Enthalpy-entropy compensation was observed in the interaction of different porphyrins with MCL, underscoring the role of water structure in the overall binding process. Analysis of CD spectra of MCL indicates that this protein contains about 13% a-helix, 36% b-sheet, 21% b-turn, and the rest unordered structures. Binding of porphyrins does not significantly alter the secondary and tertiary structures of MCL.

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“…A number of lectin -drug conjugates have also been prepared and some were successful when tested on cultured cells and animal models [32][33][34]. In view of the considerable affinity of TCSL for Cu(II)-and Zn(II)-porphyrins investigated in this study, it is possible to use the lectin as a vehicle for targeting porphyrin-based drugs to tumour tissues in PDT.…”

mentioning

confidence: 99%

Thermodynamic and kinetic analysis of porphyrin binding to Trichosanthes cucumerina seed lectin

et al. 2001

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The interaction of several metallo-porphyrins with the galactose-specific lectin from Trichosanthes cucumeirna (TCSL) has been investigated. Difference absorption spectroscopy revealed that significant changes occur in the Soret band region of the porphyrins upon binding to TCSL and these changes have been monitored to obtain association constants (K a ) and stoichiometry of binding (n ). The dimeric lectin binds two porphyrin molecules and the presence of the specific saccharide lactose did not affect porphyrin binding significantly, indicating that the sugar and the porphyrin bind at different sites. The K a values obtained for the binding of different porphyrins with TCSL at 25 8C were in the range of 2 Â 10 3 25 Â 10 5 M 21 . Association constants for meso-tetra(4-sulphonatophenyl)porphyrinato copper(II) (CuTPPS), a porphyrin bearing four negative charges and meso-tetra(4-methylpyridinium)porphyrinato copper(II) (CuTMPyP), a porphyrin with four positive charges, were determined at several temperatures; from the temperature dependence of the association constants, the thermodynamic parameters change in enthalpy (DH8) and change in entropy (DS8) associated with the binding process were estimated. The thermodynamic data indicate that porphyrin binding to TCSL is driven largely by a favourable entropic contribution; the enthalpic contribution is very small, suggesting that the binding process is governed primarily by hydrophobic forces. Stopped-flow spectroscopic measurements show that binding of CuTMPyP to TCSL takes place by a single-step process and at 20 8C, the association and dissociation rate constants were 1.89 Â 10 4 M 21 : s 21 and 0.29 s 21, respectively.

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Concanavalin A as a carrier of daunomycin

Cited by 65 publications

References 2 publications

Interaction of peanut agglutinin with normal human lymphocytes and with leukemic cells.

Interaction of peanut agglutinin with normal human lymphocytes and with leukemic cells.

Thermodynamic analysis of porphyrin binding to Momordica charantia (bitter gourd) lectin

Thermodynamic and kinetic analysis of porphyrin binding to Trichosanthes cucumerina seed lectin

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