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Polyamines pp 493–503Cite as

Measurement of Polyamine pK a Values

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 720))

Abstract

The extent of ionization of the polyamines is an important factor in their interactions with cellular components. The pKa is the pH at which a functional group is 50% ionized. For compounds such as polyamines with more than one ionizable center (atom or functional group), there is a pKa value for each center of ionization. This chapter describes the pKa values for each amine group in many important polyamines, the factors influencing these values and methods for their determination using potentiometric titration and nuclear magnetic resonance spectroscopy.

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References

  1. Henderson LJ (1908) Concerning the relationship between the strength of acids and their capacity to preserve neutrality. Am J Physiol 21:173–179

    CAS  Google Scholar 

  2. Henderson LJ (1908) The theory of neutrality regulation in the animal organism. Am J Physiol 21:427–448

    Google Scholar 

  3. Hasselbalch KA (1916) Die Berechnung der Wasserstoffzahl des Blutes aus der freien und gebundenen Kohlensäure desselben, und die Sauerstoffbindung des Blutes als Funktion der Wasserstoffzahl. Biochem Z 78:112–144

    CAS  Google Scholar 

  4. Po N, Senozan M (2001) Henderson–Hasselbalch equation: its history and limitations. J Chem Educ 78:1499–1503

    Article  CAS  Google Scholar 

  5. Frassineti C, Ghelli S, Gans P, Sabatini A, Moruzzi MS, Vacca A (1995) Nuclear ­magnetic resonance as a tool for determining protonation constants of natural polyprotic bases in solution. Anal Biochem 231:374–382

    Article  PubMed  CAS  Google Scholar 

  6. Meloun M, Bordovská S (2007) Benchmarking and validating algorithms that estimate pKa values of drugs based on their molecular structures. Anal Bioanal Chem 389:1267–1281

    Article  PubMed  CAS  Google Scholar 

  7. Basu HS, Schwietert HCA, Feuerstein BG, Marton LJ (1990) Effects of variation in the structure of spermine on the association with DNA and the induction of DNA conformational changes. Biochem J 269:329–334

    PubMed  CAS  Google Scholar 

  8. Usherwood PNR, Blagbrough IS (1989) Amino acid synapses and receptors. In: McFarlane NR (ed) Progress and prospects in insect control, Monograph No 43. Farnham, London, pp 45–58

    Google Scholar 

  9. Usherwood PNR, Blagbrough IS (1989) Antagonism of insect muscle glutamate receptors - with particular reference to arthropod toxins. In: Narahashi T, Chambers JE (eds) Insecticide action from molecule to organism, ACS Symposium Series. Plenum, New York, pp 13–31

    Google Scholar 

  10. Usherwood PNR, Sudan H, Standley C, Blagbrough IS, Bycroft BW, Mather AJ (1990) The mechanisms of neurotoxicity of low molecular weight spider toxins. In: Volans GN, Sims J, Sullivan FM, Turner P (eds) Basic science in toxicology. Taylor & Francis, London, pp 569–579

    Google Scholar 

  11. Usherwood PNR, Blagbrough IS (1991) Spider toxins affecting glutamate receptors: polyamines in therapeutic neurochemistry. Pharmacol Ther 52:245–268

    Article  PubMed  CAS  Google Scholar 

  12. Usherwood PNR, Blagbrough IS, Brackley PTH, Kerry CJ, Sudan HL, Nakanishi K (1992) Polyamines and polyamine-containing toxins - modulators and antagonists of excitatory amino acid receptors. In: Kawai N, Nakajima T, Barnard E (eds) Neuroreceptors, ion channels and the brain. Elsevier, Amsterdam, pp 11–20

    Google Scholar 

  13. Usherwood PNR, Blagbrough IS (1994) Electrophysiology of polyamines and polyamine amides. In: Carter C (ed) The neuropharmacology of polyamines. Academic, London, pp 185–204

    Google Scholar 

  14. Bergeron RJ, McManis JS, Weimar WR, Schreier KM, Gao FL, Wu QH, Ortiz-Ocasio J, Luchetta GR, Porter C, Vinson JRT (1995) The role of charge in polyamine analog recognition. J Med Chem 38:2278–2285

    Article  PubMed  Google Scholar 

  15. Leroy D, Heriche JK, Filhol O, Chambaz EM, Cochet C (1997) Binding of polyamines to an autonomous domain of the regulatory subunit of protein kinase CK2 induces a conformational change in the holoenzyme – a proposed role for the kinase stimulation. J Biol Chem 272:20820–20827

    Article  PubMed  CAS  Google Scholar 

  16. Ouameur A, Mangier E, Diamantoglou S, Rouillon R, Carpentier R, Tajmir-Riahi H (2004) Effects of organic and inorganic polyamine cations on the structure of human serum albumin. Biopolymers 73:503–509

    Article  PubMed  CAS  Google Scholar 

  17. Ahmed OAA, Pourzand C, Blagbrough IS (2006) Varying the unsaturation in N4, N9-dioctadecanoyl spermines: nonviral lipopolyamine vectors for more efficient plasmid DNA formulation. Pharm Res 23:31–40

    Article  PubMed  CAS  Google Scholar 

  18. Rege K, Ladiwala A, Hu SH, Breneman CM, Dordick JS, Cramer SM (2005) Investigation of DNA-binding properties of an aminoglycoside-polyamine library using quantitative structure-activity relationship (QSAR) models. J Chem Inf Model 45:1854–1863

    Article  PubMed  CAS  Google Scholar 

  19. Perrin DD (1965) Dissociation constants of organic bases in aqueous solution Butterworths, London, p 137

    Google Scholar 

  20. Albert A, Serjeant EP (1971) The determination of ionization constants. Chapman & Hall, London, pp 91–96

    Google Scholar 

  21. Baillon JG, Mamont PS, Wagner J, Gerhart F, Lux P (1988) Fluorinated analogs of spermidine as substrates of spermine synthase. Eur J Biochem 176:237–242

    Article  PubMed  CAS  Google Scholar 

  22. Kimberly MM, Goldstein JH (1981) Determination of pKa values and total proton distribution pattern of spermidine by Carbon-13 nuclear magnetic resonance titrations. Anal Chem 53:789–793

    Article  CAS  Google Scholar 

  23. Palmer BN, Powell HKJ (1974) Polyamine complexes with seven-membered chelate rings: Complex formation of 3-azaheptane-1,7-diamine, 4-azaoctane-1,8-diamine (spermidine), and 4,9-diazadodecane-1,12-diamine (spermine) with copper(II) and hydrogen ions in aqueous solution. J Chem Soc Dalton Trans 2089–2092

    Google Scholar 

  24. Frassineti C, Alderighi L, Gans P, Sabatini A, Vacca A, Ghelli S (2003) Determination of protonation constants of some fluorinated polyamines by means of 13C NMR data ­processed by the new computer program HypNMR2000. Protonation sequence in polyamines. Anal Bioanal Chem 376:1041–1052

    Article  PubMed  CAS  Google Scholar 

  25. Takeda Y, Samejima K, Nagano K, Watanabe M, Sugeta H, Kyogoku Y (1983) Determination of protonation sites in thermospermine and in some other polyamines by 15N and 13C nuclear magnetic resonance spectroscopy. Eur J Biochem 130:383–389

    Article  Google Scholar 

  26. Palmer BN, Powell HKJ (1974) Complex formation between 4,9-diazadodecane-1,12-diamine (spermine) and copper(II) ions and protons in aqueous solution. J Chem Soc Dalton Trans 2086–2089

    Google Scholar 

  27. Geall AJ, Taylor RJ, Earll ME, Eaton MAW, Blagbrough IS (2000) Synthesis of cholesteryl polyamine carbamates: pK a studies and condensation of calf thymus DNA. Bioconjug Chem 11:314–326

    Article  PubMed  CAS  Google Scholar 

  28. Szczepanik W, Kaczmarek P, Sobczak J, Bal W, Gatner K, Jezowska-Bojczuk M (2002) Copper(II) binding by kanamycin A and hydrogen peroxide activation by resulting complexes. New J Chem 26:1507–1514

    Google Scholar 

  29. Clouet-d’Orval B, Stage TK, Uhlenbeck OC (1995) Neomycin inhibition of the hammerhead ribozyme involves ionic interactions. Biochemistry 34:11186–11190

    Google Scholar 

  30. Geall AJ, Blagbrough IS (2000) Rapid and sensitive ethidium bromide fluorescence quenching assay of polyamine conjugate-DNA interactions for the analysis of lipoplex formation in gene therapy. J Pharm Biomed Anal 22:849–859

    Article  PubMed  CAS  Google Scholar 

  31. Glasoe PK, Long FA (1960) Use of glass electrodes to measure acidities in deuterium oxide. J Phys Chem 64:188–190

    Article  CAS  Google Scholar 

  32. Remy J-S, Sirlin C, Vierling P, Behr J-P (1994) Gene transfer with a series of lipophilic ­DNA-binding molecules. Bioconjug Chem 5:647–654

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We thank the BBSRC (A.J.G.) and the Egyptian Government (A.A.M.) for PhD studentships and Celltech Therapeutics, Slough, UK for a CASE award (to A.J.G.).

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Authors and Affiliations

  1. Department of Pharmacy and Pharmacology, University of Bath, Bath, UK

    Ian S. Blagbrough, Abdelkader A. Metwally & Andrew J. Geall

Authors
  1. Ian S. Blagbrough
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  2. Abdelkader A. Metwally
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  3. Andrew J. Geall
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Editor information

Editors and Affiliations

  1. College of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, University Drive 500, Hershey, 17033-0850, Pennsylvania, USA

    Anthony E. Pegg

  2. School of Medicine, Sidney Kimmel Comprehensive, Johns Hopkins University, Orleans St. 1650, Baltimore, 21231, Maryland, USA

    Robert A. Casero, Jr.

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Blagbrough, I.S., Metwally, A.A., Geall, A.J. (2011). Measurement of Polyamine pK a Values. In: Pegg, A., Casero, Jr., R. (eds) Polyamines. Methods in Molecular Biology, vol 720. Humana Press. https://doi.org/10.1007/978-1-61779-034-8_32

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  • DOI: https://doi.org/10.1007/978-1-61779-034-8_32

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-033-1

  • Online ISBN: 978-1-61779-034-8

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