Abstract:Polyamine induced aggregation of various DNAs has been studied under conditions usually employed in many enzymatic assays where DNA is one of the substrates. Spermine was by far the most efficient polyamine in causing aggregation followed by spermidine and cadaverine. All double-stranded and naturally occurring single-stranded DNAs were found to aggregate. No aggregation of single-stranded homodeoxypolymers could be detected under the same conditions. The concentration of polyamine at which the aggregation com… Show more
“…We measured [8]270 as a function of NaCl concentration in 25,30,35,40,45,50,55,60,63,65,68,70, and 77% ethanol. In the range of 35-60% ethanol we obtained curves similar to that shown in Fig.…”
SynopsisThe conformational response of calf thymus DNA to solvent conditions altered by varying amounts of ethanol and NaCl has been monitored by circular dichroism (CD). These measurements, which extend over a much greater range of conditions than previously examined, reveal (above critical concentrations of ethanol and salt) a condensed form of the macromolecule with unusually large positive ellipticity in the 250-300-nm region [the "(+) state]. Mere increase in NaCl concentration a t constant 35% (v/v) concentration of ethanol suffices to convert such "(+) samples-via a series of intermediate forms with CD spectra resembling those of A-DNA, then B-DNA-into "(-) states having anomalously large negative ellipticity similar to the well-known *(-) forms produced by above-critical concentrations of poly-(ethylene oxide) and salt. These ethanoUsalt-induced transitions are all completely reversible and can occur without formation of any visible precipitates. We suggest that they represent predominantly tertiary structural changes of B-form DNA molecules analogous to the changes which occur in several other systems where *(+) + *(-) interconversion has been reported. A "skein-of-yarn'' model for the condensed tertiary (and quaternary, i.e., aggregated) state of the DNA affords one possible explanation for the inversions of ellipticity in all these cases. Such a model accords well with the accepted description of cholesteric liquid crystals.
“…We measured [8]270 as a function of NaCl concentration in 25,30,35,40,45,50,55,60,63,65,68,70, and 77% ethanol. In the range of 35-60% ethanol we obtained curves similar to that shown in Fig.…”
SynopsisThe conformational response of calf thymus DNA to solvent conditions altered by varying amounts of ethanol and NaCl has been monitored by circular dichroism (CD). These measurements, which extend over a much greater range of conditions than previously examined, reveal (above critical concentrations of ethanol and salt) a condensed form of the macromolecule with unusually large positive ellipticity in the 250-300-nm region [the "(+) state]. Mere increase in NaCl concentration a t constant 35% (v/v) concentration of ethanol suffices to convert such "(+) samples-via a series of intermediate forms with CD spectra resembling those of A-DNA, then B-DNA-into "(-) states having anomalously large negative ellipticity similar to the well-known *(-) forms produced by above-critical concentrations of poly-(ethylene oxide) and salt. These ethanoUsalt-induced transitions are all completely reversible and can occur without formation of any visible precipitates. We suggest that they represent predominantly tertiary structural changes of B-form DNA molecules analogous to the changes which occur in several other systems where *(+) + *(-) interconversion has been reported. A "skein-of-yarn'' model for the condensed tertiary (and quaternary, i.e., aggregated) state of the DNA affords one possible explanation for the inversions of ellipticity in all these cases. Such a model accords well with the accepted description of cholesteric liquid crystals.
“…Data for F-actin taken from 30, 49 , for CSA13 from 67 , LL37 from 94, 99 , vimentin from 82, 114 , Pf1 from 12 , fd from 115 , Lys18 from 30 , F-actin/spermine from 14 , DNA and spermine from 116 , DNA and cobalt hexamine from 117 .…”
“…1). The rationale behind the synthesis of oligoamines is the well-known fact that spermine (a tetramine), at a concentration range of 0.05 to 0.1 mM and at near physiological ionic strength, leads to the collapse of DNA (29). Oligoamines were found to condense DNA at much lower concentrations (2 to 4 M) and are indeed powerful inhibitors of human tumor cell proliferation.…”
Microsporidia are eukaryotic obligate intracellular protists that are emerging pathogens in immunocompromised hosts, such as patients with AIDS or patients who have undergone organ transplantation. We have demonstrated in vitro and in vivo that synthetic polyamine analogs are effective antimicrosporidial agents with a broad therapeutic window. CD8-knockout mice or nude mice infected with the microsporidian Encephalitozoon cuniculi were cured when they were treated with four different novel polyamine analogs at doses ranging from 1.25 to 5 mg/kg of body weight/day for a total of 10 days. Cured animals demonstrated no evidence of parasitemia by either PCR or histologic staining of tissues 30 days after untreated control animals died.
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