Browsing by keyword "Polyamines"

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    • Polyamine analogues: potent inducers of nucleosomal array oligomerization and inhibitors of yeast cell growth
      Carruthers, Lenny M.; Marton, Laurence J.; Peterson, Craig L. (2007-04-13)
      Polyamines are naturally occurring intracellular polycations that are essential for viability and growth of eukaryotes. Dysregulation of polyamine metabolism is a hallmark of cancer and the carcinogenic process, and consequently development of polyamine analogues has emerged as a viable strategy for therapeutic intervention. Previously, we showed that the naturally occurring polyamines spermidine and spermine were quite effective at inducing the oligomerization of nucleosomal arrays in vitro, suggesting that polyamines may play a key role in regulating higher order chromatin structures in vivo. Here, we analyse the ability of a number of synthetic polyamine analogues to potentiate formation of higher order chromatin structures in vitro. We find that a class of long-chain polyamines called oligoamines are potent inducers of nucleosomal array oligomerization in vitro and that these same polyamine analogues rapidly block yeast cell growth.

    • Synthesis and in vitro characterization of a dendrimer-MORF conjugate for amplification pretargeting
      Chen, Xiangji; Dou, Shuping; Liu, Guozheng; Liu, Xinrong; Wang, Yi; Chen, Ling; Rusckowski, Mary; Hnatowich, Donald J. (2008-07-24)
      Amplification pretargeting can play an important role in molecular imaging by significantly increasing the accumulation of signal in target tissues. Multiple-step amplification pretargeting offers the potential to greatly improve target localization of effector molecules through the intermediate use of polymers conjugated with multiple copies of complementary oligomers. In this study, PAMAM dendrimer generation 3 (G3) was conjugated with multiple copies of a phosphorodiamidate morpholino (MORF) oligomer. Characterization of the conjugate by native-PAGE and SE-HPLC demonstrated that the conjugation was successful. The average numbers of MORF groups in the G3-MORF conjugate, both attached and accessible to the (99m)Tc labeled complementary MORF (cMORF), were determined. The antitumor antibody CC49 was conjugated with both MORF and cMORF (collectively (c)MORF) at an average of about one group per molecule. Nine of the 32 carboxyl groups of the dendrimer were modified with MORF, of which 90% were accessible in solution to (99m)Tc-cMORF. After purification, the G3-MORF was radiolabeled with tracer (99m)Tc-labeled cMORF (i.e., G3-MORF/(99m)Tc-cMORF) and added to the antibody CC49 previously conjugated with cMORF (i.e., CC49-cMORF/G3-MORF/(99m)Tc-cMORF), the complex demonstrated a single peak on SE-HPLC as evidence of complete hybridization between G3-MORF/(99m)Tc-cMORF and CC49-cMORF. The CC49-(c)MORF were bound to both Protein G and Protein L coated plates, and G3-MORF was added to hybridize with CC49-cMORF before the (99m)Tc-cMORF was added to test amplification pretargeting. In comparison to conventional pretargeting without the G3-MORF, the signal was amplified about 6 and 14 times, respectively, showing that the G3-MORF participated in amplifying the signal. Further amplification studies using the CC49-(c)MORF for LS174T tumor cells in tissue culture also demonstrated clear evidence of signal amplification.