LARCH ARABINOGALACTAN FOR HEPATIC DRUG-DELIVERY - ISOLATION AND CHARACTERIZATION OF A 9 KDA ARABINOGALACTAN FRAGMENT

被引:38
作者
PRESCOTT, JH [1 ]
ENRIQUEZ, P [1 ]
JUNG, C [1 ]
MENZ, E [1 ]
GROMAN, EV [1 ]
机构
[1] ADV MAGNET INC,CAMBRIDGE,MA 02138
关键词
ARABINOGALACTAN; HEPATIC DRUG DELIVERY;
D O I
10.1016/0008-6215(95)00241-2
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Purified arabinogalactan [AG(37 kDa)] from Larix occidentalis is composed of repeating units of similar molecular weight and composition. A 9 kDa arabinogalactan [AG(9 kDa)] has been obtained in high yield from AG(37 kDa) either by autoclaving at 121 degrees C or by exposure to alkaline solution in the presence of sodium borohydride. The weight average molecular weight of AG(37 kDa) was determined to be 37 and 38 kDa by intensity light scattering and sedimentation equilibrium, respectively. The weight average molecular weight of AG(9 kDa) was determined to be 9.1 and 9.5 kDa by intensity light scattering and sedimentation equilibrium, respectively. MALDI-TOF mass spectrometry yielded a molecular weight at the peak of the distribution of 8.3 kDa for AG(9 kDa). Both AG(37 kDa) and AG(9 kDa) exhibited narrow molecular-weight distributions (M(W)/M(n) similar to 1.2). AG(37 kDa) and AG(9 kDa) exhibit nearly identical C-13-NMR spectra, monosaccharide composition, and sugar linkages. It is proposed that AG(37 kDa) is composed of covalently bound subunits of AG(9 kDa). AG(37 kDa) and AG(9 kDa) bind isolated hepatocyte asialoglycoprotein receptor equally well. As a result AG(9 kDa) is a candidate for use in hepatocyte directed drug delivery and may be more desirable for such use than is AG(37 kDa).
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页码:113 / 128
页数:16
相关论文
共 30 条
[1]  
Groman, Enriquez, Jung, Josephson, Bioconjugate Chem., 5, pp. 547-556, (1994)
[2]  
Enriquez, Jung, Josephson, Tennant, Bioconjugate Chem., 6, pp. 195-202, (1995)
[3]  
Clarke, Anderson, Stone, Phytochemistry, 18, pp. 521-540, (1979)
[4]  
Churms, Merrifield, Stephen, Carbohydr. Res., 64, pp. C1-C2, (1978)
[5]  
Cowie, Polymers Chemistry and Physics of Modern Materials, pp. 146-167, (1973)
[6]  
Schachman, Methods Enzymol., 4, pp. 32-103, (1957)
[7]  
York, Methods Enzymol., 118, pp. 3-40, (1985)
[8]  
White, Kennedy, Carbohydrate Analysis, a Practical Approach, pp. 37-54, (1986)
[9]  
Hudgin, Pricer, Ashwell, Stockert, Morell, J. Biol. Chem., 249, pp. 5536-5543, (1974)
[10]  
Saito, Miyata, Sasaki, A13C Nuclear Magnetic Resonance Study of Gel-Forming (1→3)-β-D-Glucans: Molecular-Weight Dependence of Helical Conformation and of the Presence of Junction Zones for Association of Primary Molecules, Macromolecules, 11, pp. 1151-1244, (1978)