NEW CONJUGATES OF ANTITUMOR ANTIBIOTIC DOXORUBICIN
145
0.13 (C); Rt 12.63 min; ESI MS: 672.27 (å + ç)+; calc.
for C33H41N3O12, 671.27; [α]2D0 + 170° (for hydrochlo-
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1
ride, c 0.05, DMSO); H NMR (CD3OD –DMSO-d6,
10 : 1), δ, ppm: 7.75 (1 H, d, H1), 7.69 (1 H, t, H2), 7.43
(1 H, d, H3), 5.26 (1 H, d, H1'), 4.96 (1 H, m, H7), 4.16
(1 H, m, H5'), 4.05 (1 H, m, H3'), 3.88 (3 H, Ò, 4-OCH3),
3.60 (1 H, t, H1"), 3.45 (1 H, d, H4'), 2.95, 2.90/2.94,
2.90 (2 H, m, H10), 2.76 (2 H, m, H5"), 2.25, 2.02/2.22,
2.05 (2 H, 2 dd, H8), 1.87, 1.68 (2 H, m, H2'), 1.68–
1.28 (6 H, 2 × (H2", H3", and H4")), 1.15 (3 H, d, H6').
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Conjugate GM–N-(L-lysyl)doxorubicin (DGM-
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N-(L-lysyl)doxorubicin (III) (0.145 g, 0.22 mmol) in
DMSO (2 ml) to pH 3.5–4.0. The resulting solution was
added to a solution of oxidized GM [~15 ml, obtained
by the procedure described above from GM (0.400 g,
2.45 mmol)]. The reaction and purification of the
DGM-2 conjugate was similar to that described for
DGM-1. After gel filtration, the solution of purified
DGM-2 was lyophilized to give 298 mg of the product
as dark-red powder soluble in water (20–25 mg/ml);
total swelling and dissolution time was 3–3.5 h. The
doxorubicin content was ~10 mass % according to UV
spectroscopy. The resulting DGM-2 contained no dox-
orubicin or N-lysyldoxorubicin according to TLC,
GPC, and dialysis data; and was identical to starting
GM by its behavior at gel filtration and dialysis under
similar conditions. The molecular mass of GGM-2
(98 kDa) was determined as described for DGM-1.
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ACKNOWLEDGMENTS
Sela, M., Eur. J. Cancer, 1978, vol. 14, pp. 1213–1220.
The authors remember with gratitude Prof. 21. Ahmad, S. and Tester, R., Abstracts of Papers, 22nd
Intern. Carbohydrate Symp., 2004, Glasgow, UK,
Abstract C37.
A.Ya. Khorlin, whose valuable advices they followed.
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