Topic
Polyamine binding
About: Polyamine binding is a research topic. Over the lifetime, 188 publications have been published within this topic receiving 9206 citations.
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TL;DR: Depletion of intracellular spermidine together with binding to functionally important polyamine binding sites are considered the main features of the compound which cause cytostatic, and at high concentrations, cytotoxic effects.
Abstract: Bis(7-amino-4-azaheptyl)dimethylsilane is a new type of aliphatic polycation with structural features resembling those of spermine. The elongation to a seven-membered carbon chain in which the central CH 2 -group was substituted by (CH3)2Si renders the molecule more lipophilic than spermine. Cells accumulate the compound via the polyamine transport system. Due to suppression of ornithine decarboxylase, de novo putrescine biosynthesis is impaired, and intracellular putrescine and spermidine concentrations are depleted. Depletion of intracellular spermidine together with binding to functionally important polyamine binding sites are considered the main features of the compound which cause cytostatic, and at high concentrations, cytotoxic effects.
12 citations
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TL;DR: The high sensitivity of the receptor ligand interaction became evident since methyl ethers with unlike-configuration of the ring junction prefer the σ1 receptor with high selectivity.
Abstract: A series of dexoxadrol (3) analogues with various substituents at position 4 of the piperidine ring has been synthesized and pharmacologically evaluated. Key steps in the synthesis are a hetero-Diels–Alder reaction of the dioxolane-derived imine 10 with Danishefsky's diene 11 and replacement of the p-methoxybenzyl protective group by a Cbz group. All possible diastereomers were synthesized, respectively. It was shown that like-configuration of the ring junction (position 2 of the piperidine ring and position 4 of the dioxolane ring) and axial orientation of the C-4 substituent are crucial for high NMDA receptor affinity. 2-(2,2-Diphenyl-1,3-dioxolan-4-yl)piperidine with a hydroxy moiety at position 4 (17d, WMS-2508, Ki = 44 nM) represents the most potent NMDA antagonist with high selectivity against σ1 and σ2 receptors, and the polyamine binding site of the NMDA receptor. The high sensitivity of the receptor ligand interaction became evident since methyl ethers with unlike-configuration of the ring junction (19a, 19b) prefer the σ1 receptor with high selectivity.
12 citations
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TL;DR: Interest has gained the possible neuroprotective efficacy of NMDA-receptor antagonists in neurological diseases such as hypoxia/ischemia, hypoglycemia, epilepsy and chronic neurodegenerative disorders (Huntington's, Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis, and AIDS encephalopathy).
Abstract: Amino acids such as L-glutamate und L-aspartate are major excitatory neurotransmitters in the mammalian central nervous system (CNS) and potential neurotoxins (excitotoxins), which can destroy central neurons by excessive activation of respective receptors. In the last three decades evidence has accumulated that excitatory amino acids (EAA) are involved in many neurological diseases and that pharmacological intervention offers prospects of novel and more effective therapies. Three different receptor types for EAA have been identified, each being named by the selective agonist to which it is preferentially sensitive, i.e. N-methyl-D-aspartate- (NMDA), kainate- and quisqualate-receptors. In this review interest is focused primarily on the NMDA-receptor, whose structure has been subject of numerous electrophysiological and biochemical studies. Today, it is well established that the NMDA-receptor-ionophore complex has an agonist binding site for glutamate, NMDA and related EAAs which is coupled with an ion channel permeable to Na+, K+, Cl- and Ca2+. Four other binding sites for glycine, phencyclidine, Mg2+ and Zn2+ have been identified which can differentially modulate the function of the NMDA receptor. An additional polyamine binding site has recently been reported. Numerous studies on experimental animals demonstrate that modulators of NMDA-mediated neurotransmission may have antiepileptic, anxiolytic, muscle-relaxant and memory-enhancing effects. Particular interest has gained the possible neuroprotective efficacy of NMDA-receptor antagonists in neurological diseases such as hypoxia/ischemia, hypoglycemia, epilepsy and chronic neurodegenerative disorders (Huntington's, Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis, and AIDS encephalopathy).(ABSTRACT TRUNCATED AT 250 WORDS)
12 citations
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TL;DR: The role for protein-protein inter-protein interaction in spermineprotein interaction is shown and the effects of polyamines on processes involving DNA are also well documented.
12 citations
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TL;DR: The incubation of micromolar concentrations of radioactive spermine with cytosol from chick duodenum leads to the formation of a non-covalent binding between s permine and a macromolecular component of the cytosols.
12 citations