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PubMed2005

The UV-damaged DNA binding protein mediates efficient targeting of the nucleotide excision repair complex to UV-induced photo lesions.

Previous studies point to the XPC-hHR23B complex as the principal initiator of global genome nucleotide excision repair (NER) pathway, responsible for the repair of UV-induced cyclobutane pyrimidine dimers (CPD) and 6-4 photoproducts (6-4PP) in human cells. However, the UV-damaged DNA binding protein (UV-DDB) has also been proposed as a damage recognition factor involved in repair of UV-photoproducts, especially CPD. Here, we show in human XP-E cells (UV-DDB deficient) that the incision complex formation at UV-induced lesions was severely diminished in locally damaged nuclear spots. Repair kinetics of CPD and 6-4PP in locally and globally UV-irradiated normal human and XP-E cells demonstrate that UV-DDB can mediate efficient targeting of XPC-hHR23B and other NER factors to 6-4PP. The data is consistent with a mechanism in which UV-DDB forms a stable complex when bound to a 6-4PP, allowing subsequent repair proteins--starting with XPC-hHR23B--to accumulate, and verify the lesion, resulting in efficient 6-4PP repair. These findings suggest that (i) UV-DDB accelerates repair of 6-4PP, and at later time points also CPD, (ii) the fraction of 6-4PP that can be bound by UV-DDB is limited due to its low cellular quantity and fast UV dependent degradation, and (iii) in the absence of UV-DDB a slow XPC-hHR23B dependent pathway is capable to repair 6-4PP, and to some extent also CPD.

Cell Nucleus↗
PubMed2004

Immunoglobulin therapy to control lung damage in patients with common variable immunodeficiency.

BACKGROUND: Lung damage progression is the most frequent condition in patients with common variable immunodeficiency (CVID). Appropriate immunoglobulin dose adjustments and follow-up guidelines to evaluate this have not been well established. OBJECTIVE: To assess the evolution of lung damage once stable residual serum levels of IgG over 600 mg/dl had been achieved. METHODS: A prospective study was conducted in 24 adult patients consecutively diagnosed with CVID, with no previous intravenous immunoglobulin (IVIG) treatment. IVIG dose, total serum IgG level, bacterial infection rate, pulmonary function tests (PFTs) and high resolution computed tomography (HRCT) of the thorax were monitored over 2 years. Moreover, outcome data were determined by measurement of chronic pulmonary disease (CPD). RESULTS: IVIG dose variability (205-372 mg/kg/21 days) to obtain the required serum IgG levels was determined. Patients with CPD needed higher doses than those without CPD (p=0.045). A significant reduction in severe and mild infections/patient-year was observed during treatment. Overall, there were no changes in PFTs and HRCT scores in patients without CPD, but both improved in patients with CPD. An increase of over 15% in overall HRCT score was detected in two patients without evidence of impairment in either clinical status or PFT values. CONCLUSIONS: Residual levels of total IgG over 600 mg/dl may help prevent progression of lung damage in patients with CVID. Levels of IgG, clinical manifestations and PFTs seem sufficient for routine follow-up. HRCT examination of the thorax, at least biennially, may help to identify patients in whom lung injury is progressing even though they may remain symptom-free and with stable PFTs.

Adult↗
PubMed2006

Crystal structure of archaeal photolyase from Sulfolobus tokodaii with two FAD molecules: implication of a novel light-harvesting cofactor.

UV exposure of DNA molecules induces serious DNA lesions. The cyclobutane pyrimidine dimer (CPD) photolyase repairs CPD-type - lesions by using the energy of visible light. Two chromophores for different roles have been found in this enzyme family; one catalyzes the CPD repair reaction and the other works as an antenna pigment that harvests photon energy. The catalytic cofactor of all known photolyases is FAD, whereas several light-harvesting cofactors are found. Currently, 5,10-methenyltetrahydrofolate (MTHF), 8-hydroxy-5-deaza-riboflavin (8-HDF) and FMN are the known light-harvesting cofactors, and some photolyases lack the chromophore. Three crystal structures of photolyases from Escherichia coli (Ec-photolyase), Anacystis nidulans (An-photolyase), and Thermus thermophilus (Tt-photolyase) have been determined; however, no archaeal photolyase structure is available. A similarity search of archaeal genomic data indicated the presence of a homologous gene, ST0889, on Sulfolobus tokodaii strain7. An enzymatic assay reveals that ST0889 encodes photolyase from S. tokodaii (St-photolyase). We have determined the crystal structure of the St-photolyase protein to confirm its structural features and to investigate the mechanism of the archaeal DNA repair system with light energy. The crystal structure of the St-photolyase is superimposed very well on the three known photolyases including the catalytic cofactor FAD. Surprisingly, another FAD molecule is found at the position of the light-harvesting cofactor. This second FAD molecule is well accommodated in the crystal structure, suggesting that FAD works as a novel light-harvesting cofactor of photolyase. In addition, two of the four CPD recognition residues in the crystal structure of An-photolyase are not found in St-photolyase, which might utilize a different mechanism to recognize the CPD from that of An-photolyase.

Amino Acid Sequence↗
PubMed2005

Evaluation of photolyase (Photosome) repair activity in human keratinocytes after a single dose of ultraviolet B irradiation using the comet assay.

Photosome is constituted of photolyases included in liposomes. Photolyase is a bacterial enzyme that can repair ultraviolet B (UVB)-induced cyclobutane pyrimidine dimers (CPD) in eukaryotic cells. A modified version of the alkaline comet assay has been set up to evaluate the repair activity of this enzyme after a single dose of UVB (312 nm, 0.06 J/cm2) in human keratinocytes. The formation of single strand breaks (SSB) induced by the UVA photoactivation of the enzyme (1.2 J/cm2) was inhibited by the pretreatment of the cells with 4 mM L-ergothioneine (ERT) during 30 min at 37 degrees C. To increase the sensitivity of the comet assay, an additional lysis was used with a buffer containing sodium dodecyl sulfate (0.5%) and proteinase K (0.1 mg/ml) for 60 min at 37 degrees C. Unrepaired CPD by photolyase were revealed by a second enzymatic treatment with T4 endonuclease V, a CPD specific glycosylase. UVB irradiation increased the SSB level in keratinocytes and additional T4NV treatment enhanced this SSB level by 1.5-2.0-fold confirming that CPD were the major base modifications generated by UVB irradiation. UVA-photoactivated Photosome repaired CPD lesions and decreased the SSB levels by 2.6-3.3-fold. Photosome could be an additional component of sunscreens to reduce the development of skin cancer.

Cells, Cultured↗
PubMed2004

[Epidemiology of Haemophilus influenzae strains identified in 2001 in France, and assessment of their susceptibility to beta-lactams].

UNLABELLED: The aim of this study was to describe the epidemiology of H. influenzae strains collected in 2001 at the National Reference Center and to evaluate their susceptibility to beta-lactams. METHODS: The demographic characteristics were recorded for each strain, then were determined their capsular serotyping (slide agglutination with specific antisera), as well as their beta-lactamase production (chromogenic cephalosporin test, Nitrocefin), and their MICs (agar dilution method on Haemophilus Test Medium) for amoxicillin (AMX), co-amoxiclav (AMC), cefpodoxime (CPD), cefaclor (CEC), cefuroxime (CXM), and cefotaxime (CTX). RESULTS: 41.3% of the 752 strains were identified in bronchial secretions, 20.6% in conjunctivitis, 11.3% in otitis media, and 11% in blood cultures. 96.3% of the strains were not capsulated and 3.7% were of type b, d, e or f. 33.8% of the strains were beta-lactamase producers (TEM type), 45.8% of these were identified in otitis pus and 27.7% in bronchial secretions. One hundred and forty-two strains (18.9%) presented reduced susceptibility to beta-lactams (modification of target) associated or not with bla+. MICs 50/90 against bla+ strains were: AMX 1/32, AMC 0.12/1, CTX 0.007/0.03, CPD 0.03/0.12, CEC 1/64, CXM 0.25/1. Against low BLNAR and bla+ strains, MICs 50/90 were: AMX 2/32, AMC 0.25/2, CTX 0.015/0.06, CPD 0.06/0.25, CEC 4/64, CXM 0.25/4. And against low BLNAR strains MICs 50/90 were: AMX 0.25/8, AMC 0.25/8, CTX 0.015/0.12, CPD 0.06/0.50, CEC 4/32, CXM 0.25/4. CONCLUSIONS: Both bla+ and modifications of PBP are widespread among strains isolated in France. CTX, and CPD remain the most active compounds whatever the resistance mechanisms.

Colony Count, Microbial↗
PubMed2004

Power Doppler ultrasound imaging for quantification of urinary bladder neck blood flow changes.

This study was designed to evaluate power Doppler imaging for assessment of urinary bladder neck blood flow in comparison with laser Doppler flowmetry (LDF) in an animal model. Transrectal power Doppler ultrasound (US) and LDF of the urinary bladder neck were performed in three anesthetized pigs during comparative cystometry. Normal saline (NaCl) was used for the first run, followed by a second run with 0.2 mol/L potassium chloride (KCl). Standardized sonographic equipment settings (Acuson Sequoia 512); MountainView, CA) were used for power Doppler imaging. Computer-assisted calculation of color pixel density (CPD) of power Doppler images was performed using Scion Image) software image analysis. Tissue perfusion units (TPU) were measured using a BLF21 laser Doppler flowmeter (Transonic Systems Inc., Ithaca, NY, USA). The power Doppler results were compared with the findings obtained by LDF. NaCl filling resulted in a mean CPD increase at the bladder neck from 18.65 (+/- 1.78) at empty bladder to 37.8 (+/- 1.84) at 100 mL and to 88.32 (+/- 1.35) at full bladder capacity (C(max)) of 270 mL, respectively. With KCl filling, a mean CPD increase from 18.65 (+/- 1.78) to 59.63 (+/- 0.5) at 100 mL and 110.82 (+/- 2.98) at full bladder capacity (270 mL) was observed. The CPD increase was significantly higher for KCl than with NaCl (p < 0.001). With NaCl filling, bladder neck blood flow increased from 22 TPU (empty) to 46 TPU (100 mL) and 62.5 TPU at C(max), compared to 22 TPU, 50 TPU and 102.5 TPU with KCl. CPD and TPU measurements showed a strong correlation at p = 0.01. In conclusion, transrectal power Doppler US image quantification is a feasible and accurate method for assessing blood flow changes in the urinary bladder neck.

Animals↗
PubMed1997

Analysis of visual dysfunctions in HIV-positive patients without retinitis.

PURPOSE: To investigate visual dysfunctions in ophthalmoscopically normal human immunodeficiency virus (HIV)-positive patients and to correlate the results to the stage of HIV disease and neuropsychological status. METHODS: Fifty-one randomly selected eyes (26 right, 25 left) of 51 HIV-positive patients with visual acuity measurements of 20/20 or better and no ophthalmoscopically detectable disorders were prospectively examined using achromatic and short-wavelength automated perimetry, color vision testing, and contrast sensitivity testing. CD4+ T-lymphocyte count, presence of systemic infection, hemoglobin, hematocrit, serum beta 2-microglobulin levels, and results of neuropsychological testing were also analyzed. RESULTS: On achromatic automated perimetry, 21.6% (11/51) of patients performed abnormally according to the mean defect and 27.5% (14/51) according to the Glaucoma Hemifield Test; 29.4% (15/51) performed abnormally on short-wave-length automated perimetry according to the mean defect and 23.5% (12/51) according to the Glaucoma Hemifield Test. On contrast sensitivity, 5.9% (3/51) of patients performed abnormally in the 1.5-cycles per degree (cpd) line, 2.0% (2/51) in the 3-cpd line, 23.5% (12/51) in the 6-cpd line, 25.5% (13/51) in the 12-cpd line, and 33.3% (17/51) in the 18-cpd line. On the Farnsworth-Munsell 100-hue test, 29.4% (15/51) of patients performed abnormally. After correction for multiple correlations, two statistically significant correlations were found: sum of log contrast sensitivity with achromatic automated perimetry and sum of log contrast sensitivity with the Farnsworth-Munsell 100-hue test. CONCLUSIONS: A significant percentage of HIV-positive patients with visual acuity of 20/20 or better and no ophthalmologic evidence of retinitis performed abnormally on visual psychophysical tests. The severity of visual dysfunction was not correlated with the stage of HIV infection or the degree of neuropsychological dysfunction.

Adult↗
PubMed1998

Stroke rehabilitation: clinical predictors of resource utilization.

OBJECTIVE: To identify predictors of rehabilitation hospital resource utilization for patients with stroke, using demographic, medical, and functional information available on admission. DESIGN: Statistical analysis of data prospectively collected from stroke rehabilitation patients. SETTING: Large, urban, academic freestanding rehabilitation facility. PARTICIPANTS: A total of 945 stroke patients consecutively admitted for acute inpatient rehabilitation. MAIN OUTCOME MEASURES: Resource utilization was measured by rehabilitation length of stay (LOS) and mean hospital charge per day (CPD). METHODS: Independent variables were organized into categories derived from four consecutive phases of clinical assessment: (1) patient referral information, (2) acute hospital record review and patient history, (3) physical examination, and (4) functional assessment. Predictors for LOS and CPD were identified separately using four stepwise multiple linear regression analyses starting with variables from the first category and adding new category data for each subsequent analysis. RESULTS: Severe neurologic impairment, as measured by Rasch-converted NIH stroke scale and lower Rasch-converted motor measure of the Functional Independence Measure (FIM) instrument predicted longer LOS (F2,824 = 231.9, p < .001). Lower Rasch-converted motor FIM instrument measure, tracheostomy, feeding tube, and a history of pneumonia, coronary artery disease, or renal failure predicted higher CPD (F6,820 = 90.2, p < .001). CONCLUSION: Stroke rehabilitation LOS and CPD are predicted by different factors. Severe impairment and motor disability are the main predictors of longer LOS; motor disability and medical comorbidities predict higher CPD. These findings will help clinicians anticipate resource needs of stroke rehabilitation patients using medical history, physical examination, and functional assessment.

Aged↗
PubMed1999

Lung function in infants with chronic pulmonary disease after severe adenoviral illness.

OBJECTIVE: To evaluate pulmonary function and bronchodilator responses in young children with chronic pulmonary disease (CPD) after a severe adenoviral lower respiratory tract infection. METHODS: Pulmonary function tests were performed in 13 patients (mean age, 1.32 +/- 0.8 years) with CPD and were compared with a control group of 13 healthy infants (mean age, 1.16 +/- 0.4 years). RESULTS: Respiratory rate, peak tidal expiratory flow (PTEF), PTEF/tidal volume, absolute time up to PTEF, time percentage to PTEF, volume percentage for PTEF, and compliance and resistance of the respiratory system were significantly affected in the CPD group. Similarly, maximal flow at functional residual capacity (V'maxFRC) was 56.0 +/- 42 mL/s and 373 +/- 107 mL/s in the CPD and control groups, respectively (P =.001). No within-group differences with baseline values or between-group differences were noted in response to treatment with ipratropium bromide or albuterol. CONCLUSION: Young children with CPD caused by adenovirus have pulmonary function changes characterized by severe obstruction and diminished lung distensibility not responsive to the administration of inhaled ipratropium bromide or albuterol.

Adenoviridae Infections↗
PubMed1996

Brassinosteroids rescue the deficiency of CYP90, a cytochrome P450, controlling cell elongation and de-etiolation in Arabidopsis.

The cpd mutation localized by T-DNA tagging on Arabidopsis chromosome 5-14.3 inhibits cell elongation controlled by the ecdysone-like brassinosteroid hormone brassinolide. The cpd mutant displays de-etiolation and derepression of light-induced genes in the dark, as well as dwarfism, male sterility, and activation of stress-regulated genes in the light. The CPD gene encodes a cytochrome P450 (CYP90) sharing homologous domains with steroid hydroxylases. The phenotype of the cpd mutant is restored to wild type both by feeding with C23-hydroxylated brassinolide precursors and by ectopic overexpression of the CPD cDNA. Brassinosteroids also compensate for different cell elongation defects of Arabidopsis det, cop, fus, and axr2 mutants, indicating that these steroids play an essential role in the regulation of plant development.

Arabidopsis↗
PubMed2003

Structural basis for phosphodependent substrate selection and orientation by the SCFCdc4 ubiquitin ligase.

Cell cycle progression depends on precise elimination of cyclins and cyclin-dependent kinase (CDK) inhibitors by the ubiquitin system. Elimination of the CDK inhibitor Sic1 by the SCFCdc4 ubiquitin ligase at the onset of S phase requires phosphorylation of Sic1 on at least six of its nine Cdc4-phosphodegron (CPD) sites. A 2.7 A X-ray crystal structure of a Skp1-Cdc4 complex bound to a high-affinity CPD phosphopeptide from human cyclin E reveals a core CPD motif, Leu-Leu-pThr-Pro, bound to an eight-bladed WD40 propeller domain in Cdc4. The low affinity of each CPD motif in Sic1 reflects structural discordance with one or more elements of the Cdc4 binding site. Reengineering of Cdc4 to reduce selection against Sic1 sequences allows ubiquitination of lower phosphorylated forms of Sic1. These features account for the observed phosphorylation threshold in Sic1 recognition and suggest an equilibrium binding mode between a single receptor site in Cdc4 and multiple low-affinity CPD sites in Sic1.

Amino Acid Motifs↗
PubMed1997

Prognostic significance of color Doppler findings in head and neck tumors.

We examined whether or not the degree of tumor vascularity in lymph node metastases as depicted by color Doppler is associated with a patient's prognosis. Cervical lymph node metastases in 25 patients with head and neck cancer were examined before combined accelerated radiotherapy and chemotherapy. The findings were quantified using a computer-assisted protocol that quantitatively describes color Doppler images by the relative color pixel density (CPD) and the color hues, which are numerically expressed by the mean color value (MCV). We found that, in the patient group with a CPD below median, the median survival was 958 days and, in the group with a higher CPD, it was 423 days (p = 0.05). The time to detection of distant metastases was 18 months with a low CPD, and 6 months with a high CPD (p = 0.05). However, the time to local or nodal progression was not different between the groups. The MCV was not correlated with prognostic data. These results indicate that, in patients with metastatic head and neck cancer, highly vascularized lymph nodes detected with color Doppler sonography may indicate a shorter survival and earlier occurrence of distant metastases.

Blood Flow Velocity↗
PubMed1999

Expression of a mammalian DNA photolyase confers light-dependent repair activity and reduces mutations of UV-irradiated shuttle vectors in xeroderma pigmentosum cells.

Photoreactivation is one of the DNA repair mechanisms to remove UV lesions from cellular DNA with a function of the DNA photolyase and visible light. Two types of photolyase specific for cyclobutane pyrimidine dimers (CPD) and for pyrimidine (6-4) pyrimidones (6-4PD) are found in nature, but neither is present in cells from placental mammals. To investigate the effect of the CPD-specific photolyase on killing and mutations induced by UV, we expressed a marsupial DNA photolyase in DNA repair-deficient group A xeroderma pigmentosum (XP-A) cells. Expression of the photolyase and visible light irradiation removed CPD from cellular DNA and elevated survival of the UV-irradiated XP-A cells, and also reduced mutation frequencies of UV-irradiated shuttle vector plasmids replicating in XP-A cells. The survival of UV-irradiated cells and mutation frequencies of UV-irradiated plasmids were not completely restored to the unirradiated levels by the removal of CPD. These results suggest that both CPD and other UV damage, probably 6-4PD, can lead to cell killing and mutations.

Base Sequence↗
PubMed1994

2.8-A structure of yeast serine carboxypeptidase.

The structure of monomeric serine carboxypeptidase from Saccharomyces cerevisiae (CPD-Y), deglycosylated by an efficient new procedure, has been determined by multiple isomorphous replacement and crystallographic refinement. The model contains 3333 non-hydrogen atoms, all 421 amino acids, 3 of 4 carbohydrate residues, 5 disulfide bridges, and 38 water molecules. The standard crystallographic R-factor is 0.162 for 10,909 reflections observed between 20.0- and 2.8-A resolution. The model has rms deviations from ideality of 0.016 A for bond lengths and 2.7 degrees for bond angles and from restrained thermal parameters of 7.9 A2. CPD-Y, which exhibits a preference for hydrophobic peptides, is distantly related to dimeric wheat serine carboxypeptidase II (CPD-WII), which has a preference for basic peptides. Comparison of the two structures suggests that substitution of hydrophobic residues in CPD-Y for negatively charged residues in CPD-WII in the binding site is largely responsible for this difference. Catalytic residues are in essentially identical configurations in the two molecules, including strained main-chain conformational angles for three active site residues (Ser 146, Gly 52, and Gly 53) and an unusual hydrogen bond between the carboxyl groups of Glu 145 and Glu 65. The binding of an inhibitor, benzylsuccinic acid, suggests that the C-terminal carboxylate binding site for peptide substrates is Asn 51, Gly 52, Glu 145, and His 397 and that the "oxyanion hole" consists of the amides of Gly 53 and Tyr 147. A surprising result of the study is that the domains consisting of residues 180-317, which form a largely alpha-helical insertion into the highly conserved cores surrounding the active site, are quite different structurally in the two molecules. It is suggested that these domains have evolved much more rapidly than other parts of the molecule and are involved in substrate recognition.

Amino Acid Sequence↗
PubMed1996

Modulation of cyclobutane pyrimidine dimer formation in a positioned nucleosome containing poly(dA.dT) tracts.

We have used a defined-sequence nucleosome to concomitantly investigate the generation and location of DNA lesions in nucleosomes and their influence on nucleosome positioning (translational and rotational setting). A 134 bp HISAT sequence from the yeast DED1 promoter, containing a polypyrimidine region (40 bp) with a T6-tract, two T5-tracts, and a T9-tract, was reconstituted in nucleosomes with a defined rotational setting. T-tracts adopt unusually rigid DNA structures in solution ("T-tract structure") and are hot spots of cyclobutane pyrimidine dimer (CPD) formation by UV light (254 nm). DNA was irradiated with UV light before or after reconstitution. The CPD yields and distribution were analyzed by cleavage with T4 endonuclease V. The rotational setting of nucleosomal DNA was characterized by DNase I digestion. With the exception of one T5-tract (1T5), the T6-, the 2T5-, and the T9-tracts formed T-tract structure in solution. T-tract structure was lost upon folding in nucleosomes, demonstrating a dominant constraint of DNA folding in nucleosomes over that of T-tract structure. CPD formation was strongly modulated by the nucleosome structure, but the CPD distribution differed from that reported for mixed-sequence DNA. CPD formation in the nucleosome had no effect on the rotational setting of nucleosomal DNA, but the rotational setting was affected when nucleosomes were assembled on damaged DNA. The toleration of DNA distortions imposed by CPDs in nucleosomes may have important implications for the recognition and repair of these damages in chromatin.

Animals↗
PubMed2003

Active species of horseradish peroxidase (HRP) and cytochrome P450: two electronic chameleons.

The active site of HRP Compound I (Cpd I) is modeled using hybrid density functional theory (UB3LYP). The effects of neighboring amino acids and of environmental polarity are included. The low-lying states have porphyrin radical cationic species (Por(*)(+)). However, since the Por(*)(+) species is a very good electron acceptor, other species, which can be either the ligand or side chain amino acid residues, may participate in electron donation to the Por(*)(+) moiety, thereby making Cpd I behave like a chemical chameleon. Thus, this behavior that was noted before for Cpd I of P450 is apparently much more wide ranging than initially appreciated. Since chemical chameleonic behavior property was found to be expressed not only in the properties of Cpd I itself, but also in its reactivity, the roots of this phenomenon are generalized. A comparative discussion of Cpd I species follows for the enzymes HRP, CcP, APX, CAT (catalase), and P450.

Binding Sites↗
PubMed2006

Proton-shuffle mechanism of O-O activation for formation of a high-valent oxo-iron species of bleomycin.

Bleomycins (BLMs) can utilize H2O2 to cleave DNA in the presence of ferric ions. DFT calculations were used to study the mechanism of O-O bond cleavage in the low-spin FeIII-hydroperoxo complex of BLM. The following alternative hypotheses were investigated using realistic structural models: (a) heterolytic cleavage of the O-O bond, generating a Compound I (Cpd I) like intermediate, formally BLM-FeV=O; (b) homolytic O-O cleavage, leading to a BLM-FeIV=O species and an OH* radical; and (c) a direct O-O cleavage/H-abstraction mechanism by ABLM. The calculations showed that (a) is a facile and viable mechanism; it involves acid-base proton reshuffle mediated by the side-chain linkers of BLM, causing thereby heterolytic cleavage of the O-O bond and generation of Cpd I. Formation of Cpd I is found to involve a barrier of 13.3 kcal/mol, which is lower than the barriers in the alternative mechanisms (b and c) that possess respective barriers of 31 and 17 kcal/mol. The so-formed Cpd I species with a radical on the side-chain linker, methylvalerate (V), adjacent to the BLM-FeIV=O complex, resembles the formation of the active species of cytochrome c peroxidase in the Poulos-Kraut proton-shuffle mechanism in heme peroxidases (Poulos, T. L.; Kraut, J. J. Biol. Chem. 1980, 255, 8199-8205). Experimental data are discussed and shown to be in accord with this proposal. It suggests that the high-valence Cpd I species of BLM participates in the DNA cleavage. This is an alternative mechanistic hypothesis to the exclusive reactivity scenario based on ABLM (FeIII-OOH).

Bleomycin↗
PubMed1992

Characterization of silkworm chlorophyll metabolites as an active photosensitizer for photodynamic therapy.

Silkworm excreta containing chlorophyll metabolites have long been used for their medicinal activities in the Far East. The major chlorophyll derivative (CpD) fraction in the Me2CO extract from the silkworm excreta exhibits strong photodynamic action on mice and human tumor cells in vitro. The main CpD component was isolated, purified, and subjected to extensive structural and characterization studies to assess its photodynamic therapeutic activity. According to the spectral analyses, the structure of the major unknown CpD was determined to be 10-hydroxypheophytin a [1]. The CpD component possessed a high quantum efficiency (50%) for the photosensitized production of singlet molecular oxygen, thus providing a molecular basis for its photodynamic therapeutic efficiency. A further advantage is that the "photooxidation/degradation" product(s) from this CpD retains all the characteristics of a photodynamic sensitizer.

Animals↗