Abstract
We characterised a novel, charge-insufficient isosteric analogue of spermine, 11-[(amino)oxy]-4,9-diaza-l-aminoundecane (AOSPM). This analogue was synthesised by displacing aminopropyl group by aminooxyethyl group, the latter having pK(a) of about 5. Charge deficiency of the AOSPM molecule was fixed at a definite atom, while pK(a) of the rest nitrogen was similar to the parent polyamine. AOSPM competed with putrescine, spermidine and spermine for the uptake into the cell, and was accumulated in the cells in high amounts when exogenous polyamine synthesis was impaired. It was not recognised by the cells as growth-promoting polyamine, since it was unable to restore growth arrest due to polyamine deprivation. Like natural spermine, this polyamine analogue prevented oxidative DNA damage. AOSPM could be used not only as a tool to study polyamine homeostasis in the cell, but may have distinct applications either as radiation protector, a stable and non-toxic inhibitor of polyamine uptake or, as an appropriate vector, to enhance the uptake of impermeable compounds into the cell. (C) 2002 Elsevier Science Inc. All rights reserved.
| Original language | English |
|---|---|
| Pages (from-to) | 649-655 |
| Number of pages | 6 |
| Journal | Biochemical Pharmacology |
| Volume | 64 |
| DOIs | |
| Publication status | Published - 2002 |
Keywords
- aminooxyspermine
- polyamine transport
- putrescine
- spermidine
- spermine
- HUMAN CANCER-CELLS
- AMINOOXY ANALOGS
- COLON-CANCER
- SPERMIDINE/SPERMINE N-1-ACETYLTRANSFERASE
- NUCLEIC-ACIDS
- DNA HYBRIDS
- PUTRESCINE
- INHIBITORS
- BIOSYNTHESIS
- METABOLISM
Cite this
Insufficiently charged isosteric analogue of spermine: interaction with polyamine metabolism and uptake, effect on Caco-2 cell growth. / Turchanova, L.; Shvetsov, A. S.; Demin, A. V.; Khomutov, A. R.; Wallace, Heather Mann; Stein, J.; Milovic, V.
In: Biochemical Pharmacology, Vol. 64, 2002, p. 649-655.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Insufficiently charged isosteric analogue of spermine: interaction with polyamine metabolism and uptake, effect on Caco-2 cell growth
AU - Turchanova, L.
AU - Shvetsov, A. S.
AU - Demin, A. V.
AU - Khomutov, A. R.
AU - Wallace, Heather Mann
AU - Stein, J.
AU - Milovic, V.
PY - 2002
Y1 - 2002
N2 - We characterised a novel, charge-insufficient isosteric analogue of spermine, 11-[(amino)oxy]-4,9-diaza-l-aminoundecane (AOSPM). This analogue was synthesised by displacing aminopropyl group by aminooxyethyl group, the latter having pK(a) of about 5. Charge deficiency of the AOSPM molecule was fixed at a definite atom, while pK(a) of the rest nitrogen was similar to the parent polyamine. AOSPM competed with putrescine, spermidine and spermine for the uptake into the cell, and was accumulated in the cells in high amounts when exogenous polyamine synthesis was impaired. It was not recognised by the cells as growth-promoting polyamine, since it was unable to restore growth arrest due to polyamine deprivation. Like natural spermine, this polyamine analogue prevented oxidative DNA damage. AOSPM could be used not only as a tool to study polyamine homeostasis in the cell, but may have distinct applications either as radiation protector, a stable and non-toxic inhibitor of polyamine uptake or, as an appropriate vector, to enhance the uptake of impermeable compounds into the cell. (C) 2002 Elsevier Science Inc. All rights reserved.
AB - We characterised a novel, charge-insufficient isosteric analogue of spermine, 11-[(amino)oxy]-4,9-diaza-l-aminoundecane (AOSPM). This analogue was synthesised by displacing aminopropyl group by aminooxyethyl group, the latter having pK(a) of about 5. Charge deficiency of the AOSPM molecule was fixed at a definite atom, while pK(a) of the rest nitrogen was similar to the parent polyamine. AOSPM competed with putrescine, spermidine and spermine for the uptake into the cell, and was accumulated in the cells in high amounts when exogenous polyamine synthesis was impaired. It was not recognised by the cells as growth-promoting polyamine, since it was unable to restore growth arrest due to polyamine deprivation. Like natural spermine, this polyamine analogue prevented oxidative DNA damage. AOSPM could be used not only as a tool to study polyamine homeostasis in the cell, but may have distinct applications either as radiation protector, a stable and non-toxic inhibitor of polyamine uptake or, as an appropriate vector, to enhance the uptake of impermeable compounds into the cell. (C) 2002 Elsevier Science Inc. All rights reserved.
KW - aminooxyspermine
KW - polyamine transport
KW - putrescine
KW - spermidine
KW - spermine
KW - HUMAN CANCER-CELLS
KW - AMINOOXY ANALOGS
KW - COLON-CANCER
KW - SPERMIDINE/SPERMINE N-1-ACETYLTRANSFERASE
KW - NUCLEIC-ACIDS
KW - DNA HYBRIDS
KW - PUTRESCINE
KW - INHIBITORS
KW - BIOSYNTHESIS
KW - METABOLISM
U2 - 10.1016/S0006-2952(02)01225-X
DO - 10.1016/S0006-2952(02)01225-X
M3 - Article
VL - 64
SP - 649
EP - 655
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
ER -