Novel quaternary ammonium salt-containing polyamines from the Agelenopsis aperta funnel-web spider

Jasys, V. John; Kelbaugh, Paul R.; Nason, Deane M.; Phillips, Douglas; Rosnack, Kenneth J.; Saccomano, Nicholas A.; Stroh, Justin G.; Volkmann, Robert A.; Forman, James T.

doi:10.1021/jo00032a039

Cited by 39 publications

(25 citation statements)

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“…Thus, the mesityl-protecting group was removed by treatment with 30% HBr in acetic acid (23), and the resulting secondary nitrogen was reprotected as the corresponding N-(p-NO 2 -Cbz) derivative (21). The phthalimide was then removed by hydrazinolysis (24), and the resulting primary amine was converted to the corresponding N-Boc derivative (25). The N-benzyl-and N-(p-NO 2 -Cbz)-protecting groups were simultaneously removed by hydrogenolysis (26) to afford a norspermine derivative in which one of the two primary nitrogens was protected.…”

Section: Methodsmentioning

confidence: 99%

Photoaffinity Labeling of a Cell Surface Polyamine Binding Protein

Felschow

MacDiarmid

Bardos

et al. 1995

Journal of Biological Chemistry

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Intracellular polyamine pools are partially maintained by an active transport apparatus that is specific for and regulated by polyamines. Although mammalian transport activity has been characterized by kinetic studies, the actual protein itself has yet to be identified, purified, or cloned. As one approach to this problem, we attempted photoaffinity labeling of plasma membrane proteins using two specifically designed and synthesized polyamine conjugates as photoprobes. The first is a spermidine conjugate bearing the photoreactive moiety 4-azidosalicylic acid at the N 4 position via an alkyl linkage, and the second is a norspermine conjugate with 4-azidosalicylic acid at the N 1 position via an acyl linkage. Labeling of murine L1210 lymphocytic leukemia cells was carried out at 4°C to promote selective alkylation of cell surface proteins. Separation of plasma membrane proteins from cells cross-linked with the N 4 -spermidine conjugate by SDS-polyacrylamide gel electrophoresis revealed two heavily labeled proteins at ϳ118 and ϳ50 kDa (designated p118 and p50, respectively). Band p118 was more well defined and much more intensely labeled. Analogous proteins were also observed in human U937 lymphoma cells. Specificity of labeling was strongly suggested by competition with polyamines and analogs during labeling and further indicated by the nearly identical labeling of the same protein by the N 1 -norspermine photoprobe but not by the unconjugated photoreagent. Neuraminidase pretreatment of L1210 cells increased mobility of the p118, suggesting that it was glycosylated and, thus, of plasma membrane origin. In transport-deficient L1210 cells, p118 and p50 were found to have a slightly higher molecular mass and were accompanied by a less distinct protein band (ϳ100 kDa). These findings indicate the presence of a polyamine binding protein at the surface of murine and human leukemia cells, which could be directly or indirectly related to the polyamine transport apparatus.

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Section: Methodsmentioning

confidence: 99%

Photoaffinity Labeling of a Cell Surface Polyamine Binding Protein

Felschow

MacDiarmid

Bardos

et al. 1995

Journal of Biological Chemistry

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“…The structural elucidations of a number of toxins including the four most abundant constituents (Agel‐489, Agel‐489a, Agel‐505, and Agel‐505a) were published the following year 64. The structures of 41 and 42 were confirmed by total synthesis,64a but the originally proposed structures of Agel‐489a and Agel‐505a,64b were later revised and shown, by total synthesis, to contain the quaternary amino functionality as shown in the structures of 43 and 44 in Scheme 65…”

Section: Acylpolyamine Toxinsmentioning

confidence: 86%

Small Molecules from Spiders Used as Chemical Probes

2011

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Spiders are important species in ecological systems and as major predators of insects they are endowed with a plethora of low-molecular-weight natural products having intriguing biological activities. The isolation and biological characterization of these entities are well established, however, only very recently have these compounds been used as templates for the design, synthesis, and biological evaluation of synthetic analogues. In contrast, the investigation of compounds responsible for chemical communication between spiders is far less developed, but recently new light has been shed onto the area of pheromones and allomones from spiders. Herein, we recapitulate these recent results, put them into perspective with previous findings, and provide an outlook for future studies of these chemotypes.

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“…Elemental analyses were performed by the Vario Elemental CHSN‐O microanalyzer, and the purity of tested compounds was >95%. Compounds 5a – b and 6a – b were prepared according to the procedures as previously reported in the literature (23,24).…”

Section: Methodsmentioning

confidence: 99%

Synthesis, Cytotoxicity, and Cell Death Profile of Polyaminoanthraquinones as Antitumor Agents

Wang

Gao

et al. 2012

Chem Biol Drug Des

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Investigation on designed polyaminoanthraquinones revealed that the anthraquinones bearing triamine motifs are generally more potent than their counterparts with diamine or tetramine motifs. Compared with the reference drug mitoxantrone (MTX), 9b and 9c exhibited better inhibitory activity on cancerous HepG2 cells and preferable cell selectivity in the further screen of normal QSG7701 cells, although they were not assimilated by cancer cells via the polyamine transporter. The presence of polyamine motifs elevated the interaction of compounds 9b and 9c with lysosomes and resulted in distinct mode of cell death. 9c and MTX could cause caspases-dependent HepG2 cell apoptotic death involving in mitochondrial membrane potential (MMP) loss, cytochrome c release, and caspase-3 activation. However, 9b, which contained only one less methylene group in the polyamine tail, produced cytotoxicity by necrosis. In conclusion, the modification of anthraquinones with polyamines may furnish potent anticancer drug candidates against hepatocellular carcinoma undergoing distinct cell death mechanisms.

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Novel quaternary ammonium salt-containing polyamines from the Agelenopsis aperta funnel-web spider

Cited by 39 publications

References 0 publications

Photoaffinity Labeling of a Cell Surface Polyamine Binding Protein

Photoaffinity Labeling of a Cell Surface Polyamine Binding Protein

Small Molecules from Spiders Used as Chemical Probes

Synthesis, Cytotoxicity, and Cell Death Profile of Polyaminoanthraquinones as Antitumor Agents

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