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At least 523 records · Page 29Linked to original sources
PubMed2004

A new polymorphism (Ser362Thr) of the L-myc gene is not associated with lung adenocarcinoma risk and prognosis.

The non-coding variation in the second intron of the L-myc gene, generating an EcoRI polymorphism, is associated with lung cancer risk and prognosis. We carried out sequence analysis of the L-myc gene in lung adenocarcinoma (ADCA) patients to identify functional polymorphisms and identified a new single nucleotide polymorphism (SNP) in the third exon of the gene causing a Ser362Thr conservative amino acid change in the C-terminus of the encoded protein. This polymorphism showed significant linkage disequilibrium with the L-myc EcoRI polymorphism located at 1751 bp distance. Genotyping of the Ser362Thr SNP in 220 Italian ADCA patients and in 230 general population controls revealed a similar low frequency (0.10-0.11) of the Thr allele in both groups. The multivariate odds ratio was 0.68 (95% confidence interval (CI) 0.38-1.22). In the ADCA patients, no significant association between the Ser/Thr polymorphism and survival was observed. Thus, the present results do not support candidacy of the L-myc Ser362Thr polymorphism for the functional polymorphism of the L-myc genomic region.

Adenocarcinoma↗
PubMedDate not supplied

MR imaging of brainstem tumors.

Eighteen patients aged 4-72 years old with brainstem tumors were studied using a 0.5 T magnetic resonance (MR) imager and a third- or fourth-generation computed tomographic (CT) scanner. MR imaging showed the brainstem to be enlarged on sagittal views in all cases; exophytic growth was seen in eight. Alterations of signal intensities were shown in most cases on spin-echo sequences using 30 and 90 msec echo times and inversion recovery techniques. It was not possible to distinguish primary from metastatic tumors. The configurations and margins of the areas with abnormal signal did not appear to correlate with the clinical behavior of the tumors. CT was able to recognize brainstem tumor in only 13 of 16 cases. In the two cases of metastases, plain CT scans were normal, but enhancement was seen after administration of contrast material in one. It appears that MR imaging is sensitive in detecting tumor enlargement and abnormal signals and is superior to CT in evaluating brainstem tumors.

Adolescent↗
PubMed2000

Comparative analysis of expressed sequences in Phytophthora sojae.

Phytophthora sojae (Kaufmann and Gerdemann) is an oomycete that causes stem and root rot on soybean (Glycine max L. Merr) plants. We have constructed three cDNA libraries using mRNA isolated from axenically grown mycelium and zoospores and from tissue isolated from plant hypocotyls 48 h after inoculation with zoospores. A total of 3,035 expressed sequence tags (ESTs) were generated from the three cDNA libraries, representing an estimated 2,189 cDNA transcripts. The ESTs were classified according to putative function based on similarity to known proteins, and were analyzed for redundancy within and among the three source libraries. Distinct expression patterns were observed for each library. By analysis of the percentage G+C content of the ESTs, we estimate that two-thirds of the ESTs from the infected plant library are derived from P. sojae cDNA transcripts. The ESTs originating from this study were also compared with a collection of Phytophthora infestans ESTs and with all other non-human ESTs to assess the similarity of the P. sojae sequences to existing EST data. This collection of cDNA libraries, ESTs, and accompanying annotation will provide a new resource for studies on oomycetes and on soybean responses to pathogen challenge.

DNA, Complementary↗
PubMed1997

Pharmacological and clinical impact of the unique molecular structure of a new plasminogen activator.

Thrombolytic therapy has been recognized as a significant improvement in the management of acute myocardial infarction. Thrombolytic agents however have been limited by short half-lives that necessitate complex administration protocols and by the potential for bleeding complications. The native t-PA molecule has since been modified in an attempt to achieve improved lytic characteristics with less risk of bleeding. Reteplase is a third-generation recombinant mutant of tissue-type plasminogen activator (t-PA) that is expressed in Escherichia coli cells and consists of the kringle 2 and the protease domains of t-PA. Compared with t-PA, reteplase has a lower fibrin binding, which may translate to improved clot penetration. As well as a longer half-life and a more rapid initiation of thrombolysis. Preclinical pharmacology studies have indicated that reteplase has potent in vivo thrombolytic activity and leads to rapid reperfusion; these findings have been confirmed by promising results obtained in large-scale clinical trials. Other new agents developed by modifying the native t-PA molecule include the n-PA and the TNK mutants of t-PA. These novel, genetically modified thrombolytic agents all lyse clots better than the native t-PA; however, they differ with respect to their half-lives and fibrin-binding activity. Although all the third-generation thrombolytic agents have shown considerable potential in improving the efficacy of thrombolytic therapy, their risk of intracranial bleeding remains problematic and is still somewhat uncertain.

Amino Acid Sequence↗
PubMed1999

Altered gene expression in fetal Down syndrome brain as revealed by the gene hunting technique of subtractive hybridization.

Information on gene expression in brain of patients with Down Syndrome (DS, trisomy 21) is limited and molecular biological research is focussing on mapping and sequencing chromosome 21. The information on gene expression in DS available follows the current concept of a gene dosage effect due to a third copy of chromosome 21 claiming overexpression of genes encoded on this chromosome. Based upon the availability of fetal brain and recent technology of gene hunting, we decided to use subtractive hybridization to evaluate differences in gene expression between DS and control brains. Subtractive hybridization was applied on two fetal brains with DS and two age and sex matched controls, 23rd week of gestation, and mRNA steady state levels were evaluated generating a subtractive library. Subtracted sequences were identified by gene bank and assigned by alignments to individual genes. We found a series of up- and downregulated sequences consisting of chromosomal transcripts, enzymes of intermediary metabolism, hormones, transporters/channels and transcription factors (TFs). We show that trisomy 21 or aneuploidy leads to the deterioration of gene expression and the derangement of transcripts describes the impairment of transport, carriers, channels, signaling, known metabolic and hormone imbalances. The dys-coordinated expression of transcription factors including homeobox genes, POU-domain TFs, helix-loop-helix-motifs, LIM domain containing TFs, leucine zippers, forkhead genes, maybe of pathophysiological significance for abnormal brain development and wiring found in patients with DS. This is the first description of the concomitant expression of a large series of sequences indicating disruption of the concerted action of genes in this disorder.

Amino Acid Sequence↗
PubMed1999

Gene expression in fetal Down syndrome brain as revealed by subtractive hybridization.

Information on gene expression in brain of patients with Down Syndrome (DS, trisomy 21) is limited and molecular biological research is focussing on mapping and sequencing chromosome 21. The information on gene expression in DS available follows the current concept of a gene dosage effect due to a third copy of chromosome 21 claiming overexpression of genes encoded on this chromosome. Based upon the availability of fetal brain and recent technology of gene hunting, we decided to use subtractive hybridization to evaluate differences in gene expression between DS and control brains. Subtractive hybridization was applied on two fetal brains with DS and two age and sex matched controls, 23rd week of gestation, and mRNA steady state levels were evaluated generating a subtractive library. Subtracted sequences were identified by gene bank and assigned by alignments to individual genes. We found a series of up- and downregulated sequences consisting of chromosomal transcripts, enzymes of intermediary metabolism, hormones, transporters/channels and transcription factors (TFs). We show that trisomy 21 or aneuploidy leads to the deterioration of gene expression and the derangement of transcripts described describes the involvement of chromosomes other than chromosome 21, explains impairment of transport, carriers, channels, signaling, known metabolic and hormones imbalances. The dys-coordinated expression of transcription factors including homeobox genes, POU-domain TFs, helix-loop-helix-motifs, LIM domain containing TFs, leucine zippers, forkhead genes, maybe of pathophysiological significance for abnormal brain development and wiring found in patients with DS. This is the first description of the concomitant expression of a large series of sequences indicating disruption of the concerted action of genes in that disorder.

Animals↗
PubMed1990

The Drosophila transcript encoded by the beta-amyloid protein precursor-like gene is restricted to the nervous system.

We have molecularly delineated a Drosophila beta-amyloid protein precursor-like (Appl) gene and analyzed its pattern of expression. Appl defines a new locus within the 1B division of the X-chromosome, a region previously shown to be important for neural development. The genomic limits of the Appl gene were defined by mapping of the Appl cDNAs. The Appl transcript spans approximately 38 kb (1 kb = 10(3) base-pairs) of genomic DNA. Genomic regions surrounding the first two exons were sequenced. The first exon contains 78 nucleotides of the coding sequence and is separated from the second exon by a approximately 21 kb intron. The second exon is 171 nucleotides long and is separated from the third exon by a approximately 7 kb intron. We present in situ RNA localization data that demonstrate that the Appl transcript is found in post-mitotic neurons in all developmental stages, in the central and peripheral nervous systems. Within the nervous system transcripts are not observed in neuroblasts, newly generated neurons and at least one class of presumed glial cells. The temporal and spatial specificity of Appl expression suggests that the gene product has a function that is common to most neurons. Appl cDNA predicts an 886-amino acid polypeptide that exhibits strong sequence similarity to the human beta-amyloid protein precursor (APP) (Rosen et al. 1989). In this paper, we compare the Appl gene expression with the pattern of expression of the beta-amyloid protein precursor (APP) gene in mammals. Furthermore, we suggest that during evolution, a neural-specific function encoded by the APP gene has been selectively maintained.

Alzheimer Disease↗
PubMed1993

Tumor-specific lysis of human renal cell carcinomas by tumor-infiltrating lymphocytes. I. HLA-A2-restricted recognition of autologous and allogeneic tumor lines.

Metastatic renal cell carcinoma (RCC), like melanoma, belongs to the small group of human tumors in which partial or complete remission has been observed in some patients after treatment with various forms of immunotherapy. In contrast to melanoma, CTL showing MHC-restricted lysis of RCC have not been easily found among tumor-infiltrating lymphocytes (TIL). This has led to the suggestion by some that responses to immunotherapy are mediated predominantly by non-MHC-restricted effector cells. We have characterized an MHC-restricted, CD8+ CTL line obtained from an uncloned TIL population of a primary RCC using a low concentration of rIL-2; in fact, these CTL represented a majority of the short-term cultured TIL population. The CTL lysed autologous tumor cells but not normal kidney cells or target cells sensitive to non-MHC-restricted effector cells. In contrast, lymphokine-activated killer (LAK) cells grown in a high concentration of rIL-2 from the patient's PBL lysed autologous tumor and normal kidney cells in addition to several allogeneic tumors. The TIL could be expanded optimally using an autologous tumor line retrovirally transduced with the human cDNA encoding IL-2. TIL were 20-fold more potent than LAK cells in eliminating the IL-2 expressing tumor cells in vitro. The cultured TIL utilized a restricted number of V alpha gene families, suggesting that they may recognize only a limited number of MHC-peptide complexes presented by autologous tumor cells. HLA-A2 was identified as an MHC restriction molecule for presentation of one tumor-derived peptide to these CTL. Only some allogeneic HLA-A2 RCC tumors were lysed. Sequencing of the second and third exons of the HLA-A2 alleles of these cells revealed that both heterogeneity in MHC and peptide availability influenced CTL recognition. These studies demonstrate that some RCC express common antigenic determinants that can be recognized by MHC-restricted CTL and open the possibility of defining the nature of RCC-derived peptides, which, combined with HLA-A2, can generate specific immune responses.

Antibodies, Monoclonal↗
PubMed1994

Multicopy GTPase center protein L12 of Arabidopsis chloroplast ribosome is encoded by a clustered nuclear gene family with the expressed members closely linked to tRNA(Pro) genes.

A conserved architectural feature of ribosomes is a protuberance (the stalk) in the large subunit, essential for ribosomal interactions with translational factors and GTP hydrolysis and generated by two dimers of L12, the only multicopy protein in ribosomes. In higher plants, the rpl12 gene for chloroplast L12 is located in the nucleus. We report here the cloning and sequencing of this nuclear gene from Arabidopsis thaliana, revealing the first gene family for a chloroplast ribosomal protein (RP). A single cluster/haploid genome of three rpl12 genes is located in the sequenced 9.1-kilobase region of the Arabidopsis genome. Two of the rpl12 genes encode identical mature proteins, and the third encodes a 25% divergent RP, although the chloroplast-targeting transit peptide in each is distinct. The rpl12 genes encoding identical RPs are closely linked at their 5' ends to identical cytosolic tRNA(Pro) genes with a < 250-base pair spacer. Reverse transcriptase polymerase chain reaction experiments with total RNA isolated from Arabidopsis (and characterization of several L12 cDNA clones) show that only the tRNA-linked rpl12 genes are expressed. We also show (by polymerase chain reaction experiments with isolated total DNA) that this tRNA(Pro)-rpl12 gene linkage is conserved in spinach (inferred to contain a single gene copy) indicating its importance. The previously described enhanced translation of spinach L12 mRNA from its two tandem AUG codons and the two functional rpl12 genes in Arabidopsis probably provide two mechanisms for generating the four copies of L12/chloroplast ribosome, qualitatively different from those attempted in eubacteria.

Amino Acid Sequence↗
PubMed2001

A non-Golgi alpha 1,2-fucosyltransferase that modifies Skp1 in the cytoplasm of Dictyostelium.

Skp1 is a subunit of the SCF-E3 ubiquitin ligase that targets cell cycle and other regulatory factors for degradation. In Dictyostelium, Skp1 is modified by a pentasaccharide containing the type 1 blood group H trisaccharide at its core. To address how the third sugar, fucose alpha1,2-linked to galactose, is attached, a proteomics strategy was applied to determine the primary structure of FT85, previously shown to copurify with the GDP-Fuc:Skp1 alpha 1,2-fucosyltransferase. Tryptic-generated peptides of FT85 were sequenced de novo using Q-TOF tandem mass spectrometry. Degenerate primers were used to amplify FT85 genomic DNA, which was further extended by a novel linker polymerase chain reaction method to yield an intronless open reading frame of 768 amino acids. Disruption of the FT85 gene by homologous recombination resulted in viable cells, which had altered light scattering properties as revealed by flow cytometry. FT85 was necessary and sufficient for Skp1 fucosylation, based on biochemical analysis of FT85 mutant cells and Escherichia coli that express FT85 recombinantly. FT85 lacks sequence motifs that characterize all other known alpha 1,2-fucosyltransferases and lacks the signal-anchor sequence that targets them to the secretory pathway. The C-terminal region of FT85 harbors motifs found in inverting Family 2 glycosyltransferase domains, and its expression in FT85 mutant cells restores fucosyltransferase activity toward a simple disaccharide substrate. Whereas most prokaryote and eukaryote Family 2 glycosyltransferases are membrane-bound and oriented toward the cytoplasm where they glycosylate lipid-linked or polysaccharide precursors prior to membrane translocation, the soluble, eukaryotic Skp1-fucosyltransferase modifies a protein that resides in the cytoplasm and nucleus.

Amino Acid Sequence↗
PubMed1993

Residues that mediate DNA binding of autoimmune antibodies.

Somatic mutations to arginine (R) are a common feature of a subset of J558 H chain genes that code for the majority of high-affinity, anti-dsDNA antibodies in autoimmune MRL/lpr mice. To examine the consequences of such amino acid substitutions on DNA binding, we reverted three somatic mutations of a prototypic anti-dsDNA H chain gene, VH3H9, and assayed the effect of those reversions by expression in a V lambda 1 L chain-only plasmacytoma line. Reversion of R53 eliminated virtually all dsDNA binding and sharply reduced ssDNA affinity. While the complete germ-line revertant of VH3H9 retained a low level of DNA binding, the substitution of R96, a product of N base addition in the third complementarity determining region (CDR3), with glycine (G) was sufficient to abolish measureable DNA specificity. Antibodies with higher affinity for DNA were generated by introducing arginines into VH3H9 at any one of four positions where somatic mutations to arginine had been identified by sequencing other anti-dsDNA J558 H chain genes. All four arginine mutants showed affinity increments consistent with their direct involvement in DNA binding, although one such mutant, K64R, required the simultaneous reversion of an adjacent aspartic acid (D) to the germ-line glycine. Two variants with three nongerm-line arginines showed further improvements in DNA affinity suggesting that their contributions to DNA binding may be additive. Molecular modeling of antibody and mutant F(ab) structures and calculations of their electrostatic potentials were used as an aid in interpreting the results and in predicting the location and size of possible combining sites.

Amino Acid Sequence↗
PubMed1993

The promoter and intron/exon structure of the human and mouse beta 3-adrenergic-receptor genes.

Transcription-start sites for the mouse and human beta 3-adrenergic-receptor mRNA have been localized in a region comprised between 150 and 200 nucleotides 5' from the ATG translation-start codon. Motifs potentially implicated in heterologous regulation of beta 3-adrenergic-receptor expression by glucocorticoids and by beta-adrenergic agonists have been identified upstream from these cap sites. In mouse, a second mRNA initiation region is postulated to exist further upstream. Comparison of the nucleotide sequences of the 3' end of the human and mouse beta 3-adrenergic-receptor genes to those of the corresponding cDNA revealed that in contrast to beta 1 and beta 2 adrenergic receptors, the beta 3-adrenergic-receptor genes comprise several exons. A large exon (1.4 kb) encodes the first 402 and 388 amino-acid residues of the human and mouse beta 3 adrenergic receptor, respectively. In man, a second exon (700 bp) contains the sequence coding for the six carboxy-terminal residues of the receptor and the entire mRNA 3' untranslated region. In mouse, a second exon (68 bp) codes for the 12 carboxy-terminal residues of the receptor and a third exon contains the beta 3-adrenergic-receptor mRNA 3' untranslated region. The use of alternate acceptor splice sites generates two forms of exon 3 (600 bp and 700 bp), yielding two beta 3-adrenergic-receptor transcripts which are differentially expressed in white and brown adipose tissues. Human beta 3-adrenergic-receptor transcripts with different 3' untranslated regions are produced by continuation of transcription beyond termination signals. Together, our results suggest that utilization of alternate promoters and/or 3' untranslated regions may allow tissue-specific regulation of beta 3-adrenergic-receptors expression.

Amino Acid Sequence↗
PubMed2003

Structural modifications of antisense oligonucleotides.

Antisense oligonucleotides are efficient tools for the inhibition of gene expression in a sequence specific way. Natural oligonucleotides are decomposed rapidly in biological systems, which strongly restrict their application. In contrast, artificial oligonucleotides are designed to be more stable against degradation than the target mRNA, which results in a catalytic effect of the drug. Modification of the phosphate linkage has been the first successful strategy for antisense drug developments and Fomivirsene the first antisense drug in therapy. The launch of Fomivirsene has resulted in a revolutionary spin off to antisense research leading to a second generation of antisense oligonucleotides, which are stable against oligonucleotide cleaving enzymes. Among these, oligonucleotides bearing an alkoxy substituent in position 2' were the most successful ones. The third generation of antisense oligonucleotides contains structure elements, which enhance the antisense action. Zwitterionic oligonucleotides show remarkable results, first, because the stability against ribozymes is largely increased, and secondly, because the electrostatic repulsion between the anionic sense and the zwitterionic antisense cords is minimized. Promising new target molecules in antisense research are oligonucleotide chimäres, which enhance the antisense action (chimäres with intercalators, chelators or polyamines) or enable an application as sequence specific detectors (chimäres with biotin, fluorescein or radioligands).

Animals↗
PubMedDate not supplied

Generation of DM-20 splice site in myelin proteolipid protein gene: a hypothesis based on analysis of the amphibian protein.

The DM-20 isoform of proteolipid protein (PLP) of central nervous system myelin is undetectable in amphibia, but readily detectable in reptiles, birds and mammals. To explain the phylogenetic origin of DM-20, it has been proposed that a donor-acceptor RNA splice site was generated by the introduction of a single base change in the codon encoding amino acid 116 of PLP. We tested this hypothesis by isolating and sequencing peptides from bullfrog PLP. One of the peptides corresponded to mammalian residues 110-122, which contain the N-terminal boundary region for the domain excluded from DM-20 in higher vertebrates. We found that the Thr115-Val116 sequence is conserved between frog and mammal. Therefore, we propose that a single base change in the third position of the codon for Thr115 would account for the appearance of the new donor-acceptor splice site. Three amino acids elsewhere in this thirteen-residue peptide were found to differ between bullfrog and mammal, which could account for the previously reported weak recognition of amphibian PLP by an antiserum specific for peptide 109-128. A second peptide from bullfrog PLP had a sequence identical to that of residues 45-52 in mammalian PLP. Our findings explain how a specific change in the myelin PLP gene could generate a new form of the PLP protein.

Amino Acid Sequence↗
PubMed1996

Unwinding of the third strand of a DNA triple helix, a novel activity of the SV40 large T-antigen helicase.

We present experiments indicating that the SV40 large T-antigen (T-ag) helicase is capable of unwinding the third strand of DNA triple helices. Intermolecular d(TC)(20)d(GA)(20)d(TC)(20) triplexes were generated by annealing, at pH 5.5, a linearized double-stranded plasmid containing a d(TC)(27).d(GA)27 tract with a (32)P-labeled oligonucleotide consisting of a d(TC)(20) tract flanked by a sequence of 15 nt at the 3'-end. The triplexes remained stable at pH 7.2, as determined by agarose gel electrophoresis and dimethyl sulfate footprinting. Incubation with the T-ag helicase caused unwinding of the d(TC)(20) tract and consequent release of the oligonucleotide, while the plasmid molecules remained double-stranded. ATP was required for this reaction and could not be replaced by the non-hydrolyzable ATP analog AMP-PNP. T-ag did not unwind similar triplexes formed with oligonucleotides containing a d(TC)(20) tract and a 5' flanking sequence or no flanking sequence. These data indicate that unwinding of DNA triplexes by the T-ag helicase must be preceded by binding of the helicase to a single-stranded 3' flanking sequence, then the enzyme migrates in a 3'--> 5' direction, using energy provided by ATP hydrolysis, and causes release of the third strand. Unwinding of DNA triplexes by helicases may be required for processes such as DNA replication, transcription, recombination and repair.

Adenosine Triphosphate↗
PubMed1985

Complete structure of the hamster alpha A crystallin gene. Reflection of an evolutionary history by means of exon shuffling.

The eye lens contains a structural protein, alpha crystallin, composed of two homologous primary gene products alpha A2 and alpha B2. In certain rodents, still another alpha crystallin polypeptide, alpha AIns, occurs, which is identical to alpha A2 except that it contains an insertion peptide between residues 63 and 64. In this paper we describe the complete alpha A crystallin gene that has been cloned from DNA isolated from Syrian golden hamster. Evidence is provided that the alpha A gene is present as a single copy in the hamster genome. The detailed organization of the gene has been established by means of DNA sequence analysis and S1 nuclease mapping, revealing that the gene consists of four exons. The first exon contains the information for the 68 base-pair long 5' non-coding region as well as the coding information for the first 63 amino acids. The second exon encodes the 23 amino acid insertion sequence, the third exon codes for amino acid 87 to 127 of the alpha AIns chain, whereas the last exon encodes the C-terminal 69 amino acids and contains the information for the 523 base-pair long 3' non-coding region. The second exon is bordered by a 3' splice junction (A X G/G X C), which deviates from the consensus for donor splice sites (A X G/G X T). This deviation is found in both hamster and mouse. An internal duplication was detected in the first exon by using a DIAGON-generated matrix for comparison. By means of similar DIAGON-generated matrices it was confirmed that the amino acids coded for by the third and fourth exons are homologous to the small heat-shock proteins of Drosophila, Caenorhabditis and soyabean. The implications of the differential splicing and the evolutionary aspects of the detected homologies are discussed.

Animals↗
PubMed1992

Purification and characterization of human truncated prorenin.

Posttranslational processing of enzymatically inactive prorenin to an active form participates in the control of the activity of a key system involved in blood pressure regulation, growth, and other important functions. The issue is complicated because renin can be produced by a number of tissues throughout the body, in addition to the kidney, but the mechanism by which they process prorenin to renin is unknown and difficult to determine because of the small amounts of renin present. In the juxtaglomerular cell of the kidney, a 43 amino acid prosegment is cleaved from the amino terminus of prorenin to generate renin of molecular weight 44,000 [Do, Y. S., Shinagawa, T., Tam, H., Inagami, T., & Hsueh, W. A. (1987) J. Biol. Chem. 262, 1037-1043]. Using human uterine lining or a recombinant human prorenin system, we employed the same approach as that used in kidney, ammonium sulfate precipitation at pH 3.1 followed by pepstatin and H-77 affinity chromatography or gel filtration, to purify to homogeneity a 45,500-MW totally active renin. The specific activity of the active truncated prorenin was 850 Goldblatt units (GU)/mg of protein for chorion-decidua renin and 946 GU/mg of protein for recombinant renin, both similar to that reported for pure human renal renin. Both forms of renin cross-reacted with an antibody generated against 44,00-MW pure human renal renin and with an antibody generated against a peptide identical to the carboxy-terminal one-third of the prosegment.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Oxidative DNA damage induced by Cu(II)-oligopeptide complexes and hydrogen peroxide.

At physiological pH values, Cu(II)-tetraglycine and Cu(II) complexes with peptides containing a histidyl residue at the N-terminal caused DNA strand breakage in the presence of H2O2, whereas Cu(II) complexes with peptides containing histidyl residue in the second or third position did not. Because of the correlation between the generation of hydroxyl radical and DNA strand scission, a mechanism for the reaction is proposed.

Amino Acid Sequence↗