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At least 793 records · Page 44Linked to original sources
PubMed1986

Condensation of chromatin: role of multivalent cations.

We have used electric dichroism to investigate the influence of multivalent cations upon the compaction of chicken erythrocyte chromatin from the unfolded, 10-nm fiber to the 30-nm solenoid and subsequent aggregation. The pattern of condensation, which consists of compaction plus aggregation, is found to be strikingly similar for a variety of cations of differing charge, including the physiologically important polyamines spermine and spermidine. With a few exceptions such as Cu2+ and Gd3+, an optimally compacted fiber with reproducible hydrodynamic properties is produced prior to the onset of aggregation. We report the concentrations of di-, tri-, and tetravalent cations required for optimal condensation; in addition, for tri- and tetravalent cations, we were able to estimate the extent of charge neutralization produced by their binding to the optimally compacted fiber. The results show that the multivalent ion concentration required for optimal compaction decreases as cationic charge increases. In addition, the effect of a mixture of dilute mono- and multivalent cations on chromatin condensation is synergistic, rather than competitive as has been found for the multivalent cation induced condensation of DNA or the B----Z conformational transition. A simple calculation indicates that the entropy of ion uptake in chromatin condensation is surprisingly constant for a range of ionic conditions; this factor may be a dominant one in determining the folding equilibrium.

Animals↗
PubMed1990

Chromomycin dimer-DNA oligomer complexes. Sequence selectivity and divalent cation specificity.

This paper reports on a solution NMR characterization of the sequence selectivity and metal ion specificity in chromomycin-DNA oligomer complexes in the presence of divalent cations. The sequence selectivity studies have focused on chromomycin complexes with the self-complementary d(A1-A2-G3-G4-C5-C6-T7-T8) duplex containing a pair of adjacent (G3-G4).(C5-C6) steps and the self-complementary d(A1-G2-G3-A4-T5-C6-C7-T8) duplex containing a pair of separated (G2-G3).(C6-C7) steps in aqueous solution. The antitumor agent (chromomycin) and nucleic acid protons have been assigned following analysis of distance connectivities in NOESY spectra and coupling connectivities in DQF-COSY spectra for both complexes in H2O and D2O solution. The observed intermolecular NOEs establish that chromomycin binds as a Mg(II)-coordinated dimer [1 Mg(II) per complex] and contacts the minor-groove edge with retention of 2-fold symmetry centered about the (G3-G4-C5-C6).(G3-G4-C5-C6) segment of the d(A2G2C2T2) duplex. By contrast, complex formation is centered about the (G2-G3-A4-T5).(A4-T5-C6-C7) segment and results in removal of the two fold symmetry of the d(AG2ATC2T) duplex. Thus, the binding of one subunit of the chromomycin dimer at its preferred (G-G).(C-C) site assists in the binding of the second subunit to the less preferred adjacent (A-T).(A-T) site. These observations suggest a hierarchy of chromomycin binding sites, with a strong site detected at the (G-G) step due to the hydrogen-bonding potential of acceptor N3 and donor NH2 groups of guanosine that line the minor groove. The divalent cation specificity has been investigated by studies on the symmetric chromomycin-d(A2G2C2T2) complex in the presence of diamagnetic Mg(II), Zn(II), and Cd(II) cations and paramagnetic Ni(II) and Co(II) cations. A comparative NOESY study of the Mg(II) and Ni(II) symmetric complexes suggests that a single tightly bound divalent cation aligns the two chromomycins in the dimer through coordination to the C1 carbonyl and C9 enolate ions on the hydrophilic edge of each aglycon ring. Secondary divalent cation binding sites involve coordination to the major-groove N7 atoms on adjacent guanosines in G-G steps. This coordination is perturbed on lowering the pH below 6.0, presumably due to protonation of the N7 atoms. The midpoint of the thermal dissociation of the symmetric complex is dependent on the divalent cation with the stability for reversible transitions decreasing in the order Mg(II) greater than Zn(II) greater than Cd(II) complexes.(ABSTRACT TRUNCATED AT 400 WORDS)

Base Sequence↗
PubMed2001

Locating monovalent cations in the grooves of B-DNA.

Here we demonstrate that monovalent cations can localize around B-DNA in geometrically regular, sequence-specific sites in oligonucleotide crystals. Positions of monovalent ions were determined from high-resolution X-ray diffraction of DNA crystals grown in the presence of thallium(I) cations (Tl(+)). Tl(+) has previously been shown to be a useful K(+) mimic. Tl(+) positions determined by refinement of model to data are consistent with positions determined using isomorphous F(Tl) - F(K) difference Fouriers and anomalous difference Fouriers. None of the observed Tl(+) sites surrounding CGCGAATTCGCG are fully occupied by Tl(+) ions. The most highly occupied sites, located within the G-tract major groove, have estimated occupancies ranging from 20% to 35%. The occupancies of the minor groove sites are estimated to be around 10%. The Tl(+) positions in general are not in direct proximity to phosphate groups. The A-tract major groove appears devoid of localized cations. The majority of the observed Tl(+) ions interact with a single duplex and so are not engaged in lattice interactions or crystal packing. The locations of the cation sites are dictated by coordination geometry, electronegative potential, avoidance of electropositive amino groups, and cation-pi interactions. It appears that partially dehydrated monovalent cations, hydrated divalent cations, and polyamines compete for a common binding region on the floor of the G-tract major groove.

Base Sequence↗
PubMed2002

Atomic force microscopy study of the effects of Mg(2+) and other divalent cations on the end-to-end DNA interactions.

Atomic force microscopy (AFM) was applied to directly visualize the end-to-end DNA interaction mediated by magnesium cations. We took advantage of the APS-mica, allowing the preparation of samples in a broad range of monovalent and divalent cations to separate the effects of Mg(2+) and Na(+) cations on the interaction of restriction DNA fragments with cohesive end. The AFM data clearly show that DNA restriction fragments with cohesive ends form substantial amount of circles in the presence of Mg(2+) cations, suggesting that Mg(2+) cations stabilize the interaction of cohesive ends. This effect depends on the MgCl(2) concentration, so that the yield of circles approaches 18% in the presence of 50 mM MgCl(2). Furthermore, we demonstrate that this conferred cohesive end stability is specific for divalent cations, as substitution of MgCl(2) with NaCl leads to a near complete loss of cohesive end stability. We further demonstrate that cohesive end stabilization is achieved by substituting Mg(2+) with Ca(2+), Mn(2+), or Zn(2+). The data obtained suggest that the end stabilization mediated by divalent cations is primarily the result of inter-base interactions rather than bridging of phosphate moieties.

Cations, Divalent↗
PubMed2004

Nucleotide-binding kinetics of Na,K-ATPase: cation dependence.

Correlation between the Na,K-ATPase affinity to ADP and the cation (its nature and concentration) present in the medium was investigated. In buffer with low ionic strength (I approximately 1 mM) high-affinity ADP binding was not observed, while a stepwise increase in the concentrations of added cation (Na(+), Tris(+), imidazole(+), N-methylglucamine(+), choline(+)) induced an increase in the ADP affinity. The effect was fully saturated at 30-50 mM for all of the cations tested. The maximal affinity for ADP was slightly higher in the presence of Na(+), Tris(+), or imidazole(+) than in the presence of N-methylglucamine(+) or choline(+) (equilibrium dissociation constant K(d) 0.2-0.3 vs 0.7 microM). The ADP dissociation rates from its complex with enzyme in the presence of Na(+) or Tris(+) were similar, implying identity of the nucleotide-binding enzyme conformations, which therefore are assigned to E(1). The ability to compete with K(+) clearly distinguished Na(+) from other cations, which speaks against the sole involvement of the transport sites in the induction of the ADP-binding E(1) conformation. Since the cations are similar in their mode of induction of the high ADP affinity but they demonstrate a pronounced difference in ability to compete with K(+), their effects cannot be combined within any scheme with only one type of cation-binding sites. We suggest that the high affinity toward nucleotide is induced by cation interactions within the protein or lipid and that these nucleotide-domain-related sites coexist with the transport sites, which bind only Na(+) or K(+).

Adenosine Diphosphate↗
PubMed1996

Mechanism of DNA release from cationic liposome/DNA complexes used in cell transfection.

To understand how DNA is released from cationic liposome/DNA complexes in cells, we investigated which biomolecules mediate release of DNA from a complex with cationic liposomes. Release from monovalent[1,2-dioleoyl-3(1)-1(trimethylammonio)propane] or multivalent (dioctadecylamidoglycylspermine) lipids was quantified by an increase of ethidium bromide (EtBr) fluorescence. Plasmid sensitivity to DNAse I degradation was examined using changes in plasmid migration on agarose gel electrophoresis. Physical separation of the DNA from the cationic lipid was confirmed and quantified on sucrose density gradients. Anionic liposomes containing compositions that mimic the cytoplasmic-facing monolayer of the plasma membrane (e.g. phosphatidylserine) rapidly released DNA from the complex. Release occurred near a 1/1 charge ratio (-/+) and was unaffected by ionic strength or ion type. Water soluble molecules with a high negative linear charge density such as dextran sulfate or heparin also released DNA. However, ionic water soluble molecules such as ATP, tRNA, DNA, poly(glutamic acid), spermidine, spermine, or histone did not, even at 100-fold charge excess (-/+). On the basis of these results, we propose that after the cationic lipid/DNA complex is internalized into cells by endocytosis it destabilizes the endosomal membrane. Destabilization induces flip-flop of anionic lipids from the cytoplasmic-facing monolayer, which laterally diffuse into the complex and form a charge neutral ion pair with the cationic lipids. This results in displacement of the DNA from the cationic lipid and release of the DNA into cytoplasm. This mechanism accounts for a variety of observations on cationic lipid/DNA complex-cell interactions.

Animals↗
PubMed1998

Structure of the potassium form of CGCGAATTCGCG: DNA deformation by electrostatic collapse around inorganic cations.

The potassium form of d(CGCGAATTCGCG) solved by X-ray diffraction to 1.75 A resolution indicates that monovalent cations penetrate the primary and secondary layers of the "spine of hydration". Both the sodium [Shui, X., McFail-Isom, L., Hu, G. G., and Williams, L. D. (1998) Biochemistry 37, 8341-8355] and the potassium forms of the dodecamer at high resolution indicate that the original description of the spine, only two layers deep and with full occupancy by water molecules, requires substantive revision. The spine is merely the bottom two layers of a four layer solvent structure. The four layers combine to form a repeating motif of fused hexagons. The top two solvent layers were not apparent from previous medium-resolution diffraction data. We propose that the narrow minor groove and axial curvature of A-tract DNA arise from localization of cations within the minor groove. In general, the results described here support a model in which most or all forces that drive DNA away from canonical B-conformation are extrinsic and arise from interaction of DNA with its environment. Intrinsic forces, originating from direct base-base interactions such as stacking, hydrogen bonding, and steric repulsion among exocyclic groups appear to be insignificant. The time-averaged positions of the ubiquitous inorganic cations that surround DNA are influenced by DNA bases. The distribution of cations depends on sequence. Regions of high and low cation density are generated spontaneously in the solvent region by heterogeneous sequence or even within the grooves of homopolymers. The regions of high and low cation density deform DNA by electrostatic collapse. Thus, the effects of small inorganic cations on DNA structure are similar to the effects of proteins.

Cations, Monovalent↗
PubMed1999

Divalent cations stabilize the alpha 1 beta 1 integrin I domain.

Recent structural and functional analyses of alpha integrin subunit I domains implicate a region in cation and ligand binding referred to as the metal ion-dependent adhesion site (MIDAS). Although the molecular interactions between Mn2+ and Mg2+ and the MIDAS region have been defined by crystallographic analyses, the role of cation in I domain function is not well understood. Recombinant alpha 1 beta 1 integrin I domain (alpha1-I domain) binds collagen in a cation-dependent manner. We have generated and characterized a panel of antibodies directed against the alpha1-I domain, and selected one (AJH10) that blocks alpha 1 beta 1 integrin function for further study. The epitope of AJH10 was localized within the loop between the alpha 3 and alpha 4 helices which contributes one of the metal coordination sites of the MIDAS structure. Kinetic analyses of antibody binding to the I domain demonstrate that divalent cation is required to stabilize the epitope. Denaturation experiments demonstrate that cation has a dramatic effect on the stabilization of the I domain structure. Mn2+ shifts the point at which the I domain denatures from 3.4 to 6.3 M urea in the presence of the denaturant, and from 49.5 to 58.6 degrees C following thermal denaturation. The structural stability provided to the alpha1-I domain by divalent cations may contribute to augmented ligand binding that occurs in the presence of these cations.

Amino Acid Sequence↗
PubMed2005

Effect of declining lake base cation concentration on freshwater critical load calculations.

Steady-state critical load models have been extensively used as the scientific underpinning for air pollution control policies in Europe and are currently being applied to other parts of the world. An important assumption of steady-state models is that critical load estimates do not change through time (or time scale of interest). The most commonly used model for estimating freshwater critical loads is the steady-state water chemistry (SSWC) model. In this study we examined changes in SSWC critical load estimates for 29 lakes in south-central Ontario using data collected 13 years apart (1985-1998), during which time bulk sulfate (SO4(2-)) deposition decreased by 35%. In lakes with the lowest base cation concentrations (<120 microequiv L(-1) Ca2+), the decrease in SO4(2-) concentration was accompanied by an approximately equivalent decrease in base cation concentration, resulting in only a minimal increase in Acid Neutralizing Capacity (ANC) during the 13-year period (median increase 1.6 microequiv L(-1)), and the median critical load for acidity (CL(A)) estimated by the SSWC model decreased by 14.6%. These changes may have been brought about by declining base cation concentrations owing to continued soil acidification in the region. In contrast, in lakes with higher base cation concentrations (>150 microequiv L(-1) Ca2+), the relative decline in base cation concentration was not as great, resulting in a larger increase in ANC (median increase 13.1 microequiv L(-1)) and an increase in the estimated CL(A) (median 5.1%). Lakes with moderate base cation concentrations (120-150 microequiv L(-1) Ca2+) exhibited an intermediate response; the median ANC increased by 8.8 microequiv L(-1) and the estimated CL-(A) decreased by 2.2%. In central Ontario, SSWC critical load estimates based on data taken only 13 years apart change quite dramatically due to changing lake base cation concentrations, and the response appears to depend on the base status of the lakes. The changing values obtained from the SSWC model have important consequences for policy decisions regarding acceptable levels of acid deposition. The application of dynamic models that take into account changes in lake/soil chemistry appears more appropriate for estimating acceptable levels of acid deposition in the region.

Cations↗
PubMed2005

A new method to estimate adsorption energies between cations and soil particles via wien effect measurements in dilute suspensions and an approximate conductivity-activity analogy.

Measurement of the Wien effect (increased electrical conductivity at strong electrical fields) in soil suspensions is proposed as the basis of a new method to characterize energy relationships between cations and soil particles. The simplified theory behind the method, the working principle of the short high-voltage pulse apparatus, and the measuring procedure are outlined briefly. The new method was used to evaluate the adsorption energies of two monovalent (Na, K) and two divalent (Ca, Cd) cations on yellow-brown soil and black soil particles, assuming an analogy between the activity of the cations and their contribution to the electrical conductivity of the suspension. Both the mean free bonding energies, deltaGbo, and the adsorption energies, deltaGad, of the cations for these two soils increased in the order: Na < K < Ca < Cd. Under the conditions of our experiments, estimated deltaGbo ranged from 4.7 to 6.4 kJ mol(-1) and from 7.0 to 8.2 kJ mol(-1) for mono- and divalent cations, respectively. The bonding energies obtained with the new method were similar to those determined previously by ionic activity measurement. The determined mean adsorption energies of cations desorbed at a field strength of 100 kV cm(-1), for example, ranged from 0.7 to 1.2 kJ mol(-1) and from 1.9 to 2.3 kJ mol(-1) for mono- and divalent cations, respectively.

Adsorption↗
PubMed2006

Effects of membrane cation transport on pH and microbial fuel cell performance.

Due to the excellent proton conductivity of Nafion membranes in polymer electrolyte membrane fuel cells (PEMFCs), Nafion has been applied also in microbial fuel cells (MFCs). In literature, however, application of Nafion in MFCs has been associated with operational problems. Nafion transports cation species other than protons as well, and in MFCs concentrations of other cation species (Na+, K+, NH4+, Ca2+, and Mg2+) are typically 10(5) times higher than the proton concentration. The objective of this study, therefore, was to quantify membrane cation transport in an operating MFC and to evaluate the consequences of this transport for MFC application on wastewaters. We observed that during operation of an MFC mainly cation species other than protons were responsible for the transport of positive charge through the membrane, which resulted in accumulation of these cations and in increased conductivity in the cathode chamber. Furthermore, protons are consumed in the cathode reaction and, consequently, transport of cation species other than protons resulted in an increased pH in the cathode chamber and a decreased MFC performance. Membrane cation transport, therefore, needs to be considered in the development of future MFC systems.

Bacteria↗
PubMed2002

Symmetry-breaking phenomena in metalloporphyrin pi-cation radicals.

Density functional theory (DFT) calculations of the energetics, molecular structures, and spin density profiles of metalloporphyrin pi-cation radicals suggest that the common practice of describing these radicals in terms of a universal A(1u)/A(2u) dichotomy is often not justified, confirming a possibility first foreseen by Prendergast and Spiro (ref 15) over a decade ago on the basis of vibrational spectroscopy and semiempirical calculations. Because of near-degeneracy of the a(1u) and a(2u) HOMOs of many metalloporphyrins, the cation radicals derived from these compounds undergo a pseudo-Jahn-Teller (pJT) distortion and are, therefore, best described as (2)A(u) with reference to the C(4h) point group, rather than as (2)A(1u) (D(4h) or (2)A(2u) (D(4h)). We find that the porphyrin cation radicals undergo a pJT distortion if the energy difference between the (2)A(1u) and (2)A(2u) pi-cation radicals, optimized under D(4h) symmetry constraints, is less than 0.15 eV. According to this criterion, metallo-porphine and metallo-OEP pi-cation radicals should always be pJT-distorted and metallo-meso-tetrahalogenoporphyrin radicals should not. For [Zn(TPP(*))](+), the (2)A(1u)/(2)A(2u) energy difference is almost exactly at the threshold of 0.15 eV, consistent with the experimental observation of both symmetry-broken and undistorted structures for this species. The (2)A(1u)/(2)A(2u) energy difference (when the molecular geometries are optimized under a D(4h) symmetry constraint) also appears to govern whether the real pJT-distorted cation radical is more A(1u)- or A(2u)-like in terms of its spin density profile. Because many metalloporphyrin pi-cation radicals exist as cofacial dimers in the crystalline phase, we examined the symmetries and structures of the model compounds [[Zn(P)](2)](+,2+) by means of DFT geometry optimizations. The results showed that dimerization has relatively little impact on the bond length alternation in the individual rings. A final interesting result, consistent with experiment, is that the bond length alternation in the delocalized mixed-valence dimer [[Zn(P)](2)](+) is about half that found for [[Zn(P)](2)](2+).

Cations↗
PubMed2006

Relative strength of cation-pi vs salt-bridge interactions: the Gtalpha(340-350) peptide/rhodopsin system.

Interactions between cationic and aromatic side chains of amino acid residues, the so-called cation-pi interaction, are thought to contribute to the overall stability of the folded structure of peptides and proteins. The transferred NOE NMR structure of the G(t)alpha(340-350) peptide bound to photoactivated rhodopsin (R*) geometrically suggests a cation-pi interaction stabilizing the structure between the epsilon-amine of Lys341 and the aromatic ring of the C-terminal residue, Phe350. This interaction has been explored by varying substituents on the phenyl ring to alter the electron density of the aromatic ring of Phe350 and observing the impact on binding of the peptide to R*. The results suggest that while a cation-pi interaction geometrically exists in the G(t)alpha(340-350) peptide when bound to R*, its energetic contribution to the stability of the receptor-bound structure is relatively insignificant, as it was not observed experimentally. The presence of an adjacent and competing salt-bridge interaction between the epsilon-amine of Lys341 and the C-terminal carboxylate of Phe350 effectively shields the charge of the ammonium group. Experimental data supporting a significant cation-pi interaction can be regained through a series of Phe350 analogues where the C-terminal carboxyl has been converted to the neutral carboxamide, thus eliminating the shielding salt-bridge. TrNOE NMR experiments confirmed the existence of the cation-pi interaction in the carboxamide analogues. Various literature estimates of the strength of cation-pi interactions, including some that estimate strengths in excess of salt-bridges, are compromised by omission of the relevant anion in the calculations.

Algorithms↗
PubMed2002

Efficient synthesis and cell-transfection properties of a new multivalent cationic lipid for nonviral gene delivery.

Lipid-mediated delivery of DNA into cells holds great promise both for gene therapy and basic research applications. This paper describes the efficient and facile synthesis and the characterization of a new multivalent cationic lipid with a double-branched headgroup structure for gene delivery applications. The synthetic scheme can be extended to give cationic lipids of different charge, spacer, or lipid chain length. The chemical and physical properties of self-assembled complexes of the cationic liposomes (CLs) with DNA give indications of why multivalent cationic lipids possess superior transfection properties. The lipid bears a headgroup with five charges in the fully protonated state, which is attached to an unsaturated double-chain hydrophobic moiety based on 3,4-dihydroxybenzoic acid. Liposomes consisting of the new multivalent lipid and the neutral lipid 1,2-dioleoyl-sn-glycerophosphatidylcholine (DOPC) were used to prepare complexes with DNA. Investigations of the structures of these complexes by optical microscopy and small-angle X-ray scattering reveal a lamellar L(alpha)(C) phase of CL-DNA complexes with the DNA molecules sandwiched between bilayers of the lipids. Experiments using plasmid DNA containing the firefly luciferase reporter gene show that these complexes efficiently transfect mammalian cells. When compared to the monovalent cationic lipid 2,3-dioleyloxypropyltrimethylammonium chloride (DOTAP), the higher charge density of the membranes of CL-DNA complexes achievable with the new multivalent lipid greatly increases transfection efficiency in the regime of small molar ratios of cationic to neutral lipid. This is desired to minimize the known toxicity effects of cationic lipids.

Animals↗
PubMed2005

Marked variations of dissociation energy and H-bond character of the guanine-cytosine base pair induced by one-electron oxidation and Li+ cation coupling.

The variation of dissociation energy and H-bond character of the G-C cation and the Li-GC cation have been investigated by employing density functional theory (B3LYP) with the 6-31+G* basis set. The one-electron oxidation and the coupling of Li(+) to the guanine-cytosine base pair can strengthen the interaction between guanine and cytosine. The interaction of the cation Li(+) with guanine is attractive and is attributed to the polarization of the H-bonds between G-C that enhances G-C interaction. The cooperativity of the three H-bonds in the GC and Li-GC cations is different from that in the neutral GC base pair. The proton-transfer process between N(1) of the guanine and N(3) of the cytosine can occur in the GC cation and the Li-GC cation. The geometries of the transition state are out of plane, especially for the transition state of the Li-GC cation. The analysis of the activation energy for the proton-transfer process shows that the GC(+) before and after proton transfer can exist simultaneously in the gas phase, but for the Li-GC(+) system, the Li-GC(+) without proton transfer is the dominating species in the gas phase.

Base Pairing↗
PubMed2005

Electrophoresis of a biocolloid covered with a cation-absorptive membrane.

The electrophoretic behavior of a biocolloid covered with a charged membrane is theoretically analyzed in the present study. Here, the influences of nonuniformly distributed fixed groups, absorption of cations by fixed original functional groups, variation in dielectric constant in the electrophoretic system, and ionic sizes are considered. The results of numerical simulation suggest that a larger absolute value of the electrophoric mobility of biocolloids could be generated by larger membrane electricity. The absolute value of the electrophoric mobility for the nonlinear distribution of the fixed groups is larger than that for the linear distribution of the fixed groups. The absolute value of the electrophoric mobility increases with (1) the concentration of total fixed groups, (2) the cation-absorption equilibrium constant, (3) the nonuniform feature index for functional-groups distribution, (4) the dielectric constants of the inner uncharged membrane zone for only mobile cationic charge and for both mobile cationic and anionic charge, and (5) the effective size of the cations. An increase in the absolute value of the electrophoric mobility can also be resulted from a decrease in the following parameters: (1) the friction coefficient of the biocolloidal membrane phase, (2) the membrane thickness, (3) the dielectric constant of space for all charge and of outer uncharged membrane zone, (4) the effective sizes of anions and fixed groups, and (5) the number of cations and the fixed original functional groups involved in the formation of a cation-functional group complex.

Absorption↗
PubMed2006

Stable gas-phase radical cations of dimeric tryptophan and tyrosine derivatives.

Stable radical cations of dimeric amino acid derivatives of tryptophan and tyrosine were generated by collision-induced dissociation of [Cu(II)(diethylenetriamine)(amino acid derivative)2]*2+. The yields of the dimer radical cations were dependent on both the auxiliary ligand and the tryptophan or tyrosine derivatives used. Amino acid derivatives with an unmodified carboxylic acid group did not generate dimer radical cations. For the amino acid derivatives Ac-Trp-OMe and Ac-Trp-NH2 (Ac is N-acetyl; OMe and NH2 are the methyl ester and amide modifications of the C-terminal carboxylic group), no auxiliary ligand was required for generating the dimer radical cations. Collision-induced dissociation of the [Cu(II)(amino acid derivative)4]*2+ precursor generated the dimer radical cation [(amino acid derivative)2]*+. Stabilizing interactions, most likely involving hydrogen bonding, between the two amino acid derivatives are proposed to account for observation of the dimer radical cations. Dissociation of these ions yields protonated or radical cationic amino acid derivatives; these observations are consistent with the expectation of proton competition between monomeric units, whose proton affinities were calculated using density functional theory.

Acetylation↗
PubMed2000

Oxygen radical-mediated pulmonary toxicity induced by some cationic liposomes.

PURPOSE: The objectives of this study are to investigate the toxicity associated with polycationic liposomes and to elucidate the underlying mechanism. We tested the hypothesis that the positive charge of liposomes is a key determinant of toxicity by testing differently charged liposomes in mice. METHODS: Differently charged liposomal systems including cationic liposomes, LipofectAMINE and DOTAP, and neutral and negative liposomes were evaluated for their toxicity after pulmonary administration in mice. LDH assay and differential cell counts were performed to measure toxicity and pulmonary inflammation, respectively. Reactive oxygen intermediates (ROI) were assessed by chemiluminescence. RESULTS: Instillation of cationic liposomes elicited dose-dependent toxicity and pulmonary inflammation. This effect was more pronounced with the multivalent cationic liposome LipofectAMINE as compared to the monovalent cationic DOTAP. Neutral and negative liposomes did not exhibit lung toxicity. Toxicity associated with cationic liposomes correlated with the oxidative burst induced by the liposomes. LipofectAMINE induced a dose-dependent increase in ROI generation. This effect was less pronounced with DOTAP and absent with neutral and negative liposomes. CONCLUSIONS: ROI play a key role in cationic lipid-mediated toxicity. Polyvalent cationic liposomes cause a release of ROI which are responsible for the pulmonary toxicity.

Animals↗