¨
M. R. Hakkinen et al.
380
Bitonti AJ, Dumont JA, Bush TL, Stemerick DM, Edwards ML,
McCann PP (1990) Bis(benzyl)polyamine analogs as novel
substrates for polyamine oxidase. J Biol Chem 265:382–388
Bolkenius FN, Seiler N (1989) New substrates of polyamine oxidase.
Dealkylation of N-alkyl-a, w-diamines. Biol Chem Hoppe Seyler
370:525–531
Byers TL, Bitonti AJ, McCann PP (1990) Bis(benzyl)polyamine
analogues are substrates for a mammalian cell-transport system
which is distinct from the polyamine-transport system. Biochem
J 269:35–40
Casero RA Jr, Marton LJ (2007) Targeting polyamine metabolism
and function in cancer and other hyperproliferative diseases. Nat
Rev Drug Discov 6:373–390
Devereux W, Wang Y, Stewart TM, Hacker A, Smith R, Frydman B,
Valasinas AL, Reddy VK, Marton LJ, Ward TD, Woster PM,
Casero RA (2003) Induction of the PAOh1/SMO polyamine
oxidase by polyamine analogues in human lung carcinoma cells.
Cancer Chemother Pharmacol 52:383–390
Edwards ML, Stemerick DM, Bitonti AJ, Dumont JA, McCann PP,
Bey P, Sjoerdsma A (1991) Antimalarial polyamine analogues.
J Med Chem 34:569–574
FDA (2001) Guidance for industry, bioanalytical method validation.
US Department of Health and Human Services Food and Drug
Administration, Center for Drug Evaluation and Research
Heby O, Persson L, Rentala M (2007) Targeting the polyamine
biosynthetic enzymes: a promising approach to therapy of
African sleeping sickness, Chagas’ disease, and leishmaniasis.
Amino Acids 33:359–366
JE (2006b) Alpha-methyl polyamines: efficient synthesis and
tolerance studies in vivo and in vitro. First evidence for dormant
stereospecificity of polyamine oxidase. J Med Chem 49:399–406
Kaiser A, Ulmer D, Goebel T, Holzgrabe U, Saeftel M, Hoerauf A
(2006) Inhibition of hypusine biosynthesis in plasmodium: a
possible, new strategy in prevention and therapy of malaria. Mini
Rev Med Chem 6:1231–1241
Lawson KR, Marek S, Linehan JA, Woster PM, Casero RA Jr, Payne
CM, Gerner EW (2002) Detoxification of the polyamine
analogue N1-ethyl-N11-[(cycloheptyl)methy]-4, 8-diazaunde-
cane (CHENSpm) by polyamine oxidase. Clin Cancer Res
8:1241–1247
Lee Y, Sayre LM (1998) Reaffirmation that metabolism of poly-
amines by bovine plasma amine oxidase occurs strictly at the
primary amino termini. J Biol Chem 273:19490–19494
Lentini A, Mattioli P, Provenzano B, Abbruzzese A, Caraglia M,
Beninati S (2007) Role of the FAD-dependent polyamine oxidase
in the selective formation of N(1), N(8)-bis(gamma-glutam-
yl)spermidine protein cross-links. Biochem Soc Trans 35:396–400
Libby PR, Porter CW (1987) Separation of two isozymes of
polyamine oxidase from murine L1210 leukemia cells. Biochem
Biophys Res Commun 144:528–535
Muller IB, Das Gupta R, Luersen K, Wrenger C, Walter RD (2008)
Assessing the polyamine metabolism of Plasmodium falciparum
as chemotherapeutic target. Mol Biochem Parasitol 160:1–7
Pegg AE (1988) Polyamine metabolism and its importance in
neoplastic growth and as a target for chemotherapy. Cancer
Res 48:759–774
Pegg AE, Feith DJ (2007) Polyamines and neoplastic growth.
Biochem Soc Trans 35:295–299
¨
¨
Hyvonen T, Keinanen TA, Khomutov AR, Khomutov RM, Eloranta
TO (1992) Monitoring of the uptake and metabolism of
aminooxy analogues of polyamines in cultured cells by high-
performance liquid chromatography. J Chromatogr 574:17–21
Pegg AE, Poulin R, Coward JK (1995) Use of aminopropyltransferase
inhibitors and of non-metabolizable analogs to study polyamine
regulation and function. Int J Biochem Cell Biol 27:425–442
Pledgie A, Huang Y, Hacker A, Zhang Z, Woster PM, Davidson NE,
Casero RA Jr (2005) Spermine oxidase SMO(PAOh1), Not N1-
acetylpolyamine oxidase PAO, is the primary source of cytotoxic
H2O2 in polyamine analogue-treated human breast cancer cell
lines. J Biol Chem 280:39843–39851
Reguera RM, Tekwani BL, Balana-Fouce R (2005) Polyamine
transport in parasites: a potential target for new antiparasitic
drug development. Comp Biochem Physiol C Toxicol Pharmacol
140:151–164
Royo M, Fitzpatrick PF (2005) Mechanistic studies of mouse
polyamine oxidase with N1, N12-bisethylspermine as a sub-
strate. Biochemistry 44:7079–7084
Seiler N (1995) Polyamine oxidase, properties and functions. Prog
Brain Res 106:333–344
Seiler N (2003) Thirty years of polyamine-related approaches to
cancer therapy. Retrospect and prospect. Part 2. Structural
analogues and derivatives. Curr Drug Targets 4:565–585
Seiler N (2004) Catabolism of polyamines. Amino Acids 26:217–233
Smith RG, Daves DG Jr (1978) New mass spectrometric rearrange-
ments involving silicon. A study of trimethylsilylated di- and
polyamines and their isotopically labeled analogues. J Org Chem
43:2178–2183
¨
¨
Hyvonen MT, Keinanen TA, Cerrada-Gimenez M, Sinervirta R,
¨ ¨
¨
Grigorenko N, Khomutov AR, Vepsalainen J, Alhonen L, Janne
J (2007) Role of hypusinated eukaryotic translation initiation
factor 5A in polyamine depletion-induced cytostasis. J Biol
Chem 282:34700–34706
¨
Hakkinen MR, Keinanen TA, Vepsalainen J, Khomutov AR, Alhonen
¨
¨
¨ ¨
S (2007) Analysis of underivatized
L, Janne J, Auriola
polyamines by reversed phase liquid chromatography with
electrospray tandem mass spectrometry. J Pharm Biomed Anal
45:625–634
¨
Hakkinen MR, Keinanen TA, Vepsalainen J, Khomutov AR, Alhonen
¨
¨
¨ ¨
L, Janne J, Auriola S (2008) Quantitative determination of
underivatized polyamines by using isotope dilution RP-LC-ESI-
MS/MS. J Pharm Biomed Anal 48:414–421
¨ ¨
Hakkinen MR, Keinanen TA, Khomutov AR, Auriola S, Weisell J,
¨
¨ ¨
Alhonen L, Janne J, Vepsalainen J (2009) Synthesis of novel
deuterium labelled derivatives of N-alkylated polyamines. Tet-
rahedron 65:547–562
¨
¨
Holtta E (1977) Oxidation of spermidine and spermine in rat liver:
purification and properties of polyamine oxidase. Biochemistry
16:91–100
¨
Jarvinen A, Grigorenko N, Khomutov AR, Hyvonen MT, Uimari A,
¨
Suzuki O, Matsumoto T, Katsumata Y (1984) Determination of
polyamine oxidase activities in human tissues. Experientia
40:838–839
¨ ¨
Vepsalainen J, Sinervirta R, Keinanen TA, Vujcic S, Alhonen L,
Porter CW, Janne J (2005) Metabolic stability of alpha -
¨
¨
methylated polyamine derivatives and their use as substitutes for
the natural polyamines. J Biol Chem 280:6595–6601
Tabor CW, Tabor H (1984) Polyamines. Ann Rev Biochem 53:749–
790
¨
Jarvinen A, Keinanen TA, Grigorenko NA, Khomutov AR, Uimari A,
¨
Tsukada T, Furusako S, Maekawa S, Hibasami H, Nakashima K
(1988) Purification by affinity chromatography and character-
ization of porcine liver cytoplasmic polyamine oxidase. Int J
Biochem 20:695–702
¨ ¨
¨
Vepsalainen J, Alhonen L, Janne J (2006a) Guide molecule-
driven stereospecific degradation of alpha-methylpolyamines by
polyamine oxidase. J Biol Chem 281:4589–4595
¨
Jarvinen AJ, Cerrada-Gimenez M, Grigorenko NA, Khomutov AR,
¨
Vujcic S, Diegelman P, Bacchi CJ, Kramer DL, Porter CW (2002)
Identification and characterization of a novel flavin-containing
¨ ¨ ¨
Vepsalainen JJ, Sinervirta RM, Keinanen TA, Alhonen LI, Janne
123