114459-62-0Relevant articles and documents
Homologation of polyamines in the rapid synthesis of lipospermine conjugates and related lipoplexes
Geall, Andrew J.,Blagbrough, Ian S.
, p. 2449 - 2460 (2000)
Lipopolyamine amides are useful cationic lipids, synthetic vectors for non-viral gene delivery. Desymmetrisation of readily available symmetrical polyamines is an important first step in the synthesis of such compounds. The application of trifluoroacetyl
Thiazole orange – Spermine conjugate: A potent human telomerase inhibitor comparable to BRACO-19
Wang, Siwen,Yang, Dazhou,Singh, Mandeep,Joo, Hyun,Rangel, Vanessa M.,Tran, Aaron,Phan, Erich,Xue, Liang
, p. 20 - 33 (2019)
In this report, we synthesized a series of TO conjugates containing different amino side chains and investigated their binding to telomeric G-quadruplex DNA (G4) using several biophysical methods including fluorometric titration and thermal denaturation monitored by fluorescence and circular dichroism. The composition of side chains strongly affects the binding of these molecules to G-quadruplex DNA. Incorporation of amino side chains increases the binding affinity of TO toward G4 but has a minimal effect on its selectivity for G4 over duplex DNA. The plausible binding modes are a synergistic effect of end-stacking and groove interactions as indicated by docking studies. Inhibition of human telomerase activity by TO derivatives was determined in vitro by the TRAP assay. Several derivatives can selectively inhibit the activity of telomerase over DNA polymerase at low concentrations. More significantly, TO-spermine conjugate (16) exhibits a remarkable effect on telomerase inhibition in the submicromolar range, which is comparable to the inhibition effect of a well-known G4 ligand, BRACO-19. Our results here provide guidance of utilizing TO derivatives as a viable scaffold to design novel G4 ligands, G4 probes, and potent telomerase inhibitors.
DNA condensation by cholesterol polyamine carbamates: A first step in gene therapy
Geall, Andrew J.,Blagbrough, Ian S.
, p. 145 - 150 (1999)
Novel cholesterol polyamine carbamates were prepared and their pKa values determined potentiometrically. Using the Henderson-Hasselbach equation, their charge, at physiological pH, was determined. Binding affinity for calf thymus DNA was measured using an
Spermine-functionalized pen lene bisimide dyes-highly fluorescent bola-amphiphiles in water
Rehm, Stefanie,Stepanenko, Vladimir,Zhang, Xin,Rehm, Thomas H.,Wuerthner, Frank
, p. 3372 - 3382 (2010)
A series of four sperminefunctionalized perylene bisimide dyes without linkers (1) and with linkers (24) between the chromophore and the polyamine was synthesized. Protonation of the spermine moieties resulted in the formation of highly water-soluble dyes with up to six positively charged ammonium ions. The aggregation behavior of these strongly fluorescent bola-amphiphiles was studied in pure water as solvent by UV/Vis and fluorescence spectroscopy, and an astonishingly high fluorescence quantum yield of up to φfl=0.90 was observed for PBI 1. Atomic force microscopy and transmission electron microscopy were applied for the visualization of the aggregates on surfaces. Molecular modeling studies were performed by force-field calculations to explore the aggregate morphologies, which also provided valuable information on the influence of the additional alkylcarbonyl linkers. Our detailed spectroscopic and microscopic investigations revealed that the excellent optical properties of perylene bisimide chromophores can be used even in pure deionized water if their aggregation is efficiently suppressed.
Evaluation method for polyamine uptake by N1-Dansylspermine
Takao, Koichi,Sugita, Yoshiaki,Shirahata, Akira
, p. 533 - 539 (2010)
Polyamine uptake by the polyamine transport system (PTS) in HTC cells was studied without the use of radioisotope-labeled polyamines. N-Dansylspermine (DNS343) was selected as a candidate probe to examine the PTS. DNS343 was incorporated into HTC cells, and its distribution in the cells was confirmed by fluorescence microscopy. The incorporation of DNS343 via PTS was confirmed by a competition study with bis(3-aminopropyl)amine, which is incorporated into cells via the PTS. In addition, the temperature dependency of DNS343 uptake and studies with inhibitors of ornithine decarboxylase and proteoglycan synthesis supported the use of DNS 343 as a fluorescent probe for the PTS. The kinetics studies for HTC cells treated with or without an ornithine decarboxylase inhibitor indicated that DNS343 uptake was saturable and that the apparent Km values for the PTS were approximately 1.5 μM in both types of cells at 37°C. Thus, we developed an assay method for the PTS by high-performance liquid-chromatography with DNS343. The inhibitory effect of polyamine analogs and related compounds on DNS343 uptake was then examined and discussed. Springer-Verlag 2009.
Cheno-, urso- and deoxycholic acid spermine conjugates: Relative binding affinities for calf thymus DNA
Blagbrough, Ian S.,Al-Hadithi, Dima,Geall, Andrew J.
, p. 3439 - 3447 (2000)
Cationic lipid polyamine amides (cholan-24-amides) have been prepared from chenodeoxycholic (3α,7α-dihydroxy), ursodeoxycholic (3α,7β- dihydroxy), and deoxycholic (3α,12α-dihydroxy) bile acids (5β-cholanes) by acylation of tri-Boc protected spermine. Their relative binding affinities for calf thymus DNA were determined using an ethidium bromide displacement assay. These lipopolyamine amides are synthetic vectors for non-viral gene delivery and models for lipoplex formation with respect to lipofection, a key first step in gene therapy. (C) 2000 Elsevier Science Ltd.
Structure-activity relationships of lipopolysaccharide sequestration in N-alkylpolyamines
Shrestha, Anurupa,Sil, Diptesh,Malladi, Subbalakshmi S.,Warshakoon, Hemamali J.,David, Sunil A.
, p. 2478 - 2481 (2009)
We have previously shown that simple N-acyl or N-alkyl polyamines bind to and sequester Gram-negative bacterial lipopolysaccharide, affording protection against lethality in animal models of endotoxicosis. Several iterative design-and-test cycles of SAR studies, including high-throughput screens, had converged on compounds with polyamine scaffolds which have been investigated extensively with reference to the number, position, and length of acyl or alkyl appendages. However, the polyamine backbone itself had not been explored sufficiently, and it was not known if incremental variations on the polymethylene spacing would affect LPS-binding and neutralization properties. We have now systematically explored the relationship between variously elongated spermidine [NH2-(CH2)3-NH-(CH2) 4-NH2] and norspermidine [NH2-(CH2)3-NH-(CH2) 3-NH2] backbones, with the N-alkyl group being held constant at C16 in order to examine if changing the spacing between the inner secondary amines may yield additional SAR information. We find that the norspermine-type compounds consistently showed higher activity compared to corresponding spermine homologues.
A benzoperylene self-assembly complex with turn-on excimer emission for wash-free cell membrane fluorescence imaging
Niu, Niu,Zhou, Huipeng,Liu, Ning,Ren, Jia,Li, Weiqing,Yu, Cong
, p. 14446 - 14449 (2019)
A rational design of a benzoperylene probe BP-3 with positive charge allows for turn-on excimer emission, and wash-free cell membrane imaging. BP-3 possesses excellent chemical, thermal and photo stability. And the Stokes shift of the excimer emission is considerably large (90-100 nm), which very much avoids the background fluorescence interference.
Synthesis of cholesterol-polyamine carbamates: PKa studies and condensation of calf thymus DNA
Geall, Andrew J.,Taylor, Richard J.,Earll, Mark E.,Eaton, Michael A. W.,Blagbrough, Ian S.
, p. 1403 - 1404 (1998)
Novel cholesterol-polyamine carbamates have been prepared and their pKas determined potentiometrically for conjugates substituted with up to five amino functional groups and the binding affinity for calf thymus DNA has also been determined; these polyamine carbamates are models for lipoplex formation with respect to gene delivery (lipofection), a key first step in gene therapy.
Direct force measurement between cucurbit[6]uril and spermine using atomic force microscopy
Kim, Jeonghan,Kim, Youngkook,Baek, Kangkyun,Ko, Young Ho,Kim, Dongwoo,Kim, Kimoon
, p. 8389 - 8393 (2008)
The rupture forces of individual host-guest complexes between surface-confined cucurbit[6]uril (CB[6]) and spermine derivatives were measured directly by atomic force microscopy (AFM). While 1,2-dithiolane-attached spermine was immobilized on a gold-coated AFM tip, perallyloxyCB[6] was attached to an allyl-terminated self-assembled monolayer on a gold substrate by olefin metathesis reaction. A histogram and autocorrelation function analysis yielded a rupture force of approximately 120 pN, which is the highest value ever reported for a synthetic host-guest system.
