| 21262304 |
Characterization of antimicrobial peptides in skin secretions from discrete populations of Lithobates chiricahuensis (Ranidae) from central and southern Arizona |
10.1016/j.peptides.2011.01.018. |
Peptides |
Characterization of antimicrobial peptides in skin secretions from discrete populations of Lithobates chiricahuensis (Ranidae) from central and southern Arizona
Abstract
- Populations of the Chiricahua leopard frog Lithobates chiricahuensis (Ranidae) occupying regions in southern Arizona (southern range) are morphologically distinct from those from the Mogollon Rim of central Arizona (northern range) and a comparison of DNA sequences of mitochondrial genes has suggested that they may represent separate species. Peptidomic analysis of norepinephrine-stimulated skin secretions has led to the identification of six peptides with antimicrobial activity in samples from specimens from both groups. The primary structure of the peptides (esculentin-2 CHa, ranatuerin-2 CHa, -CHb, and -CHc, and brevinin-1 CHa and -CHb) isolated from both southern and northern range frogs are identical consistent with the proposal that the two populations are conspecific. However, palustrin-2CHa and the atypical brevinin-1 CHc (FFPTIAG*****LTKLFCA ITKKC), containing a five amino acid residue deletion, were identified only in secretions from southern range specimens. Consequently, there is some support for the proposal that the two populations are closely related but separate species but this support is relatively weak. Esculentin-2 CHa (GFSSIFRGVAKFASKGLG KDLAKLGVDLVACKISKQC) displayed the highest antimicrobial potency (MIC ≤ 10μM) against a variety of microorganisms and was only moderately hemolytic (LC(50) = 150 μM). Cladistic analysis based upon the primary structures of brevinin-1 peptides indicates a close phylogenetic relationship between L. chiricahuensis, L. onca, and L. yavapaiensis.
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| 21269460 |
Initial characterization of the human central proteome. |
10.1186/1752-0509-5-17 |
BMC Syst. Biol. |
Initial characterization of the human central proteome.
Abstract
- Background: On the basis of large proteomics datasets measured from seven human cell lines we consider their intersection as an approximation of the human central proteome, which is the set of proteins ubiquitously expressed in all human cells. Composition and properties of the central proteome are investigated through bioinformatics analyses.
Results: We experimentally identify a central proteome comprising 1,124 proteins that are ubiquitously and abundantly expressed in human cells using state of the art mass spectrometry and protein identification bioinformatics. The main represented functions are proteostasis, primary metabolism and proliferation. We further characterize the central proteome considering gene structures, conservation, interaction networks, pathways, drug targets, and coordination of biological processes. Among other new findings, we show that the central proteome is encoded by exon-rich genes, indicating an increased regulatory flexibility through alternative splicing to adapt to multiple environments, and that the protein interaction network linking the central proteome is very efficient for synchronizing translation with other biological processes. Surprisingly, at least 10% of the central proteome has no or very limited functional annotation. Conclusions: Our data and analysis provide a new and deeper description of the human central proteome compared to previous
Results thereby extending and complementing our knowledge of commonly expressed human proteins. All the data are made publicly available to help other researchers who, for instance, need to compare or link focused datasets to a common background.
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| 21295070 |
Host defense peptides in skin secretions of the Oregon spotted frog Rana pretiosa: implications for species resistance to chytridiomycosis |
10.1016/j.dci.2011.01.017. |
Dev Comp Immunol |
Host defense peptides in skin secretions of the Oregon spotted frog Rana pretiosa: implications for species resistance to chytridiomycosis
Abstract
- Population declines due to chytridiomycosis among frogs belonging to the Amerana (Rana boylii) species group from western North America have been particularly severe. Norepinephrine-stimulated skin secretions from the Oregon spotted frog Rana pretiosa Baird and Girard, 1853 were collected from individuals that had been previously infected with the causative agent Batrachochytrium dendrobatidis but had proved resistant to developing chytridiomycosis. These secretions contained a more diverse array of antimicrobial peptides than found in other species from the Amerana group and 14 peptides were isolated in pure form. Determination of their primary structures identified the peptides as esculentin-2PRa and -2PRb; ranatuerin-2PRa, -2PRb, -2PRc, -2PRd, and -2PRe; brevinin-1PRa, -1PRb, -1PRc, and -1PRd; and temporin-PRa, -PRb, and -PRc. The strongly cationic ranatuerin-2PRd and the esculentin-2 peptides, which have not been identified in the secretions of other Amerana species except for the closely related R. luteiventris, showed the highest growth inhibitory potency against microorganisms. The strongly hydrophobic brevinin-1PRd was the most cytotoxic to erythrocytes. Although no clear correlation exists between production of dermal antimicrobial peptides by a species and its resistance to fatal chytridiomycosis, the diversity of these peptides in R. pretiosa may be pivotal in defending the species against environmental pathogens such as B. dendrobatidis.
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| 21299113 |
Isolation and characterization of crotosparsamide, a new cyclic nonapeptide from Croton sparsiflorus |
None |
Nat Prod Commun |
Isolation and characterization of crotosparsamide, a new cyclic nonapeptide from Croton sparsiflorus
Abstract
- Crotosparsamide (1), a new cyclic nonapeptide, has been isolated from the n-butanol soluble sub-fraction of Croton sparsiflorus along with p-hydroxy methylcinnamate and kaempferol, which are reported for the first time from this species. Their structures were determined by chemical and spectral studies including ESIMS, and 1D and 2D NMR spectroscopic data.
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| 21326252 |
A new anti-MRSA antibiotic complex, WAP-8294A II. Structure characterization of minor components by ESI LCMS and MS/MS |
10.1038/ja.2011.9. |
J Antibiot (Tokyo) |
A new anti-MRSA antibiotic complex, WAP-8294A II. Structure characterization of minor components by ESI LCMS and MS/MS
Abstract
- The anti-MRSA antibiotic, WAP-8294A, was isolated from the fermentation broth of Lysobacter sp. The major component, WAP-8294A2, is composed of 1 mol of Gly, L-Leu, L-Glu, D-Asn, D-Trp, D-threo-β-hydroxyasparagine, N-Me-D-Phe and N-Me-L-Val, and 2 mol of L-Ser, D-Orn and D-3-hydroxy-7-Me-octanoic acid. The structure of the WAP-8294A2 was mainly determined as a cyclic depsipeptide by 2D NMR experiments. However, it was difficult to use the NMR experiment to determine the minor components, A1, A4 and Ax13, isolated in small amounts. In the present study, ESI MS/MS was applied to the structure elucidation of these minor components. The structures of these minor components were determined on the basis of the fragmentation pattern of the product ions of WAP-8294A2 in the ESI MS/MS. As a result, it was confirmed that A1 and A4 had the same amino acid sequence as A2, while A1 and A4 had the 3-OH-octanoic acid and 3-OH-8-Me-nonanoic acid, respectively, in the place of the 3-OH-7-Me-octanoic acid in A2. In the structure of Ax13, it was found that Gly of A2 was changed to β-Ala of Ax13.
|
| 21341718 |
Malyngamide 3 and cocosamides A and B from the marine cyanobacterium Lyngbya majuscula from Cocos Lagoon, Guam |
10.1021/np1008015. |
J Nat Prod |
Malyngamide 3 and cocosamides A and B from the marine cyanobacterium Lyngbya majuscula from Cocos Lagoon, Guam
Abstract
- Malyngamide 3 (1) and cocosamides A (2) and B (3) were isolated from the lipophilic extract of a collection of Lyngbya majuscula from Cocos Lagoon, Guam. The planar structures of compounds 1-3 were determined by spectroscopic methods. The absolute configuration of 1 was determined by modified Mosher's method, NOESY data, and comparison with lyngbic acid (4). The absolute configurations of 2 and 3 were assigned by enantioselective HPLC analysis and comparison with the closely related compound pitipeptolide A (5). Compounds 1-3 showed weak cytotoxicity against MCF7 breast cancer and HT-29 colon cancer cells.
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| 21348454 |
Acyldepsipeptide HDAC inhibitor production induced in Burkholderia thailandensis |
10.1021/ol200225v. |
Org Lett |
Acyldepsipeptide HDAC inhibitor production induced in Burkholderia thailandensis
Abstract
- Natural product gene clusters are often tightly regulated, resulting in gene cluster silencing in laboratory fermentation studies. The systematic overexpression of transcription factors (TFs) associated with biosynthetic gene clusters found in the genome of Burkholderia thailandensis E264 identified a set of TFs that, when overexpressed, alter the secondary metabolome of this bacterium. The isolation and characterization of burkholdacs A and B, two new acyldepsitripeptide histone deacetylase inhibitors produced by B. thailandensis overexpressing the TF bhcM, is reported.
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| 21361040 |
[Elucidating the structure of two cyclotides of Viola tianshanica maxim by MALDI TOF/TOF MS analysis] |
None |
Yao Xue Xue Bao |
[Elucidating the structure of two cyclotides of Viola tianshanica maxim by MALDI TOF/TOF MS analysis]
Abstract
- The cyclotides are a family of cyclic "mini" proteins that occur in Violaceae, Rubiaceae and Cucurbitaceae plant families and contain a head-to-tail cyclic backbone and a cystine knot arranged by three disulfide bonds. To study the natural cyclotides of V tianshanica, dried herb was extracted with 50% ethanol, and the concentrated aqueous extract was subjected to a solvent-solvent partitioning between water and hexane, ethyl acetate and n-butanol, separately. The n-butanol extract containing cyclotides was subjected to column chromatography over Sephadex LH-20, eluted with 30% methanol. The subfractions were directly reduced by DTT and analyzed by reverse-phase HPLC. The peaks with different retention times were shown on the profile of RP-HPLC and collected. The cyclotides were speculated based on masses range from 3 000 to 3 500 Da. The purified cyclotides were reduced with DTT, alkylated with iodoacetamide, and then were cleaved with endoproteinase Glu-C, endoproteinase Lys-C and Trypsin, separately. The digested peptides were purified on RP-HPLC and analyzed on MALDI TOF/TOF analyzer. A new cyclotide, cycloviolacin T1 and a reported cyclotide varv E were systemically determined using MALDI TOF/TOF system. So the method for the isolation and characterization of cyclotides was quickly built up in succession.
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| 21396894 |
Application of high-speed counter-current chromatography for preparative separation of cyclic peptides from Vaccaria segetalis |
10.1016/j.jchromb.2011.02.001. |
J Chromatogr B Analyt Technol Biomed Life Sci |
Application of high-speed counter-current chromatography for preparative separation of cyclic peptides from Vaccaria segetalis
Abstract
- Following an initial clean-up step on silica gel, high-speed counter-current chromatography (HSCCC) was used to separate cyclic peptides from an extract of the seeds of Vaccaria segetalis. The two-phase solvent system used for HSCCC separation was composed of petroleum ether-ethyl acetate-methanol-water at an optimized volume ratio of 0.5:3.5:1:5. From 190 mg of crude extract, 38.0 mg of segetalin B and 28.5 mg of segetalin A were obtained with purities of 98.1% and 95.6% as determined by HPLC, respectively. The chemical structures of the target compounds were confirmed by high resolution electrospray ionization time of flight MS (HRESI-TOF-MS) and (1)H NMR analyses.
|
| 21396976 |
Limctins: a new class of antimicrobial peptides from the skin secretion of the Fujian large-headed frog (Limctes fujianensis) |
10.1016/j.biochi.2011.03.003. |
Biochimie |
Limctins: a new class of antimicrobial peptides from the skin secretion of the Fujian large-headed frog (Limctes fujianensis)
Abstract
- Amphibian skin secretions are rich sources of biologically-active peptides with antimicrobial peptides predominating in many species. Several studies involving molecular cloning of biosynthetic precursor-encoding cDNAs from skin or skin secretions have revealed that these exhibit highly-conserved domain architectures with an unusually high degree of conserved nucleotide and resultant amino acid sequences within the signal peptides. This high degree of nucleotide sequence conservation has permitted the design of primers complementary to such sites facilitating "shotgun" cloning of skin or skin secretion-derived cDNA libraries from hitherto unstudied species. Here we have used such an approach using a skin secretion-derived cDNA library from an unstudied species of Chinese frog - the Fujian large-headed frog, Limctes fujianensis - and have discovered two 16-mer peptides of novel primary structures, named limctin-1Fa (SFPFFPPGICKRLKRC) and limctin-1Fb (SFHVFPPWMCKSLKKC), that represent the prototypes of a new class of amphibian skin antimicrobial peptide. Unusually these limctins display activity only against a Gram-negative bacterium (MICs of 35 and 70 μM) and are devoid of haemolytic activity at concentrations up to 160 μM. Thus the "shotgun" cloning approach described can exploit the unusually high degree of nucleotide conservation in signal peptide-encoding domains of amphibian defensive skin secretion peptide precursor-encoding cDNAs to rapidly expedite the discovery of novel and functional defensive peptides in a manner that circumvents specimen sacrifice without compromising robustness of data.
|
| 21406692 |
System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. |
10.1126/scisignal.2001570 |
Sci. Signal. |
System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
Abstract
- To elucidate cellular events underlying the pluripotency of human embryonic stem cells (hESCs), we performed parallel quantitative proteomic and phosphoproteomic analyses of hESCs during differentiation initiated by a diacylglycerol analog or transfer to media that had not been conditioned by feeder cells. We profiled 6521 proteins and 23,522 phosphorylation sites, of which almost 50% displayed dynamic changes in phosphorylation status during 24 hours of differentiation. These data are a resource for studies of the events associated with the maintenance of hESC pluripotency and those accompanying their differentiation. From these data, we identified a core hESC phosphoproteome of sites with similar robust changes in response to the two distinct treatments. These sites exhibited distinct dynamic phosphorylation patterns, which were linked to known or predicted kinases on the basis of the matching sequence motif. In addition to identifying previously unknown phosphorylation sites on factors associated with differentiation, such as kinases and transcription factors, we observed dynamic phosphorylation of DNA methyltransferases (DNMTs). We found a specific interaction of DNMTs during early differentiation with the PAF1 (polymerase-associated factor 1) transcriptional elongation complex, which binds to promoters of the pluripotency and known DNMT target genes encoding OCT4 and NANOG, thereby providing a possible molecular link for the silencing of these genes during differentiation.
|
| 21411496 |
Pharmacological characterization of FE 202158, a novel, potent, selective, and short-acting peptidic vasopressin V1a receptor full agonist for the treatment of vasodilatory hypotension |
10.1124/jpet.111.178848. |
J Pharmacol Exp Ther |
Pharmacological characterization of FE 202158, a novel, potent, selective, and short-acting peptidic vasopressin V1a receptor full agonist for the treatment of vasodilatory hypotension
Abstract
- FE 202158, ([Phe(2),Ile(3),Hgn(4),Orn(iPr)(8)]vasopressin, where Hgn is homoglutamine and iPr is isopropyl), a peptidic analog of the vasoconstrictor hormone [Arg(8)]vasopressin (AVP), was designed to be a potent, selective, and short-acting vasopressin type 1a receptor (V(1a)R) agonist. In functional reporter gene assays, FE 202158 was a potent and selective human V(1a)R agonist [EC(50) = 2.4 nM; selectivity ratio of 1:142:1107:440 versus human vasopressin type 1b receptor, vasopressin type 2 receptor (V(2)R), and oxytocin receptor, respectively] contrasting with AVP's lack of selectivity, especially versus the V(2)R (selectivity ratio of 1:18:0.2:92; human V(1a)R EC(50) = 0.24 nM). This activity and selectivity profile was confirmed in radioligand binding assays. FE 202158 was a potent vasoconstrictor in the isolated rat common iliac artery ex vivo (EC(50) = 3.6 nM versus 0.8 nM for AVP) and reduced rat ear skin blood flow after intravenous infusion in vivo (ED(50) = 4.0 versus 3.4 pmol/kg/min for AVP). The duration of its vasopressor effect by intravenous bolus in rats was as short as AVP at submaximally effective doses. FE 202158 had no V(2)R-mediated antidiuretic activity in rats by intravenous infusion at its ED(50) for reduction of ear skin blood flow, in contrast with the pronounced antidiuretic effect of AVP. Thus, FE 202158 seems suitable for treatment of conditions where V(1a)R activity is desirable but V(2)R activity is potentially deleterious, such as vasodilatory hypotension in septic shock. In addition to the desirable selectivity profile, its short-acting nature should allow dose titration with rapid onset and offset of action to optimize vasoconstriction efficacy and safety.
|
| 21414779 |
Discovery of 2,4-bis-arylamino-1,3-pyrimidines as insulin-like growth factor-1 receptor (IGF-1R) inhibitors |
10.1016/j.bmcl.2011.02.075. |
Bioorg Med Chem Lett |
Discovery of 2,4-bis-arylamino-1,3-pyrimidines as insulin-like growth factor-1 receptor (IGF-1R) inhibitors
Abstract
- The insulin-like growth factor-1 receptor (IGF-1R) plays an important role in the regulation of cell growth and differentiation, and in protection from apoptosis. IGF-1R has been shown to be an appealing target for the treatment of human cancer. Herein, we report the synthesis, structure-activity relationships (SAR), X-ray cocrystal structure and in vivo tumor study results for a series of 2,4-bis-arylamino-1,3-pyrimidines.
|
| 21420695 |
Cyclopeptide alkaloids from Scutia buxifolia Reiss |
10.1016/j.phytochem.2011.02.019. |
Phytochemistry |
Cyclopeptide alkaloids from Scutia buxifolia Reiss
Abstract
- Scutianene E (1), 3,4,28-tris-epi-scutiaene E (2), 28-epi-scutianene E (3) and scutianene L (4), four neutral cyclopeptide alkaloids, were isolated from Scutia buxifolia Reiss, together with four known cyclopeptide alkaloids, scutianines B, C, D and E. Scutianenes 1-3 are diastereoisomeric compounds, with 3-hydroxyleucine as a β-hydroxy amino acid unit, which is connected to the styryl fragment via an ether bridge, β-phenylserine, as a common ring-bonded amino acid residue. Attached to the amino group of β-hydroxyamino acid is a side chain [trans-CH=CH-Ph]. The structures of the peptides were elucidated by means of spectroscopic analysis, including extensive 2D NMR studies. The stereochemistry for the diastereomeric 3,4,28-tris-epi-scutiaene E and 28-epi-scutianene E was confirmed by X-ray diffraction analysis of their O-acetyl derivatives.
|
| 21423169 |
Albumins and their processing machinery are hijacked for cyclic peptides in sunflower |
10.1038/nchembio.542. |
Nat Chem Biol |
Albumins and their processing machinery are hijacked for cyclic peptides in sunflower
Abstract
- The cyclic peptide sunflower trypsin inhibitor 1 (SFTI-1) blocks trypsin and is a promising drug lead and protein engineering scaffold. We show that SFTI-1 and the newfound SFT-L1 are buried within PawS1 and PawS2, precursors for seed storage protein albumins. Proalbumins are matured by asparaginyl endopeptidase, which we show is required to liberate both ends of SFTI-1 as well as to mature PawS1 albumin. Thus, these peptides emerge from within an albumin precursor by the action of albumin's own processing enzyme.
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