BMC chemical biology最新文献

{"title":"Electronic properties of amino acid side chains: quantum mechanics calculation of substituent effects.","authors":"Donard S Dwyer","doi":"10.1186/1472-6769-5-2","DOIUrl":"https://doi.org/10.1186/1472-6769-5-2","url":null,"abstract":"<p><strong>Background: </strong>Electronic properties of amino acid side chains such as inductive and field effects have not been characterized in any detail. Quantum mechanics (QM) calculations and fundamental equations that account for substituent effects may provide insight into these important properties. PM3 analysis of electron distribution and polarizability was used to derive quantitative scales that describe steric factors, inductive effects, resonance effects, and field effects of amino acid side chains.</p><p><strong>Results: </strong>These studies revealed that: (1) different semiempirical QM methods yield similar results for the electronic effects of side chain groups, (2) polarizability, which reflects molecular deformability, represents steric factors in electronic terms, and (3) inductive effects contribute to the propensity of an amino acid for alpha-helices.</p><p><strong>Conclusion: </strong>The data provide initial characterization of the substituent effects of amino acid side chains and suggest that these properties affect electron density along the peptide backbone.</p>","PeriodicalId":80682,"journal":{"name":"BMC chemical biology","volume":"5 ","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2005-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6769-5-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25230094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of ERK Activity Sensor, an in vitro, FRET-based sensor of Extracellular Regulated Kinase activity.","authors":"Harry M Green,&nbsp;José Alberola-Ila","doi":"10.1186/1472-6769-5-1","DOIUrl":"https://doi.org/10.1186/1472-6769-5-1","url":null,"abstract":"<p><strong>Background: </strong>Study of ERK activation has thus far relied on biochemical assays that are limited to the use of phospho-specific antibodies and radioactivity in vitro, and analysis of whole cell populations in vivo. As with many systems, fluorescence resonance energy transfer (FRET) can be utilized to make highly sensitive detectors of molecular activity. Here we introduce FRET-based ERK Activity Sensors, which utilize variants of Enhanced Green Fluorescent Protein fused by an ERK-specific peptide linker to detect ERK2 activity.</p><p><strong>Results: </strong>ERK Activity Sensors display varying changes in FRET upon phosphorylation by active ERK2 in vitro depending on the composition of ERK-specific peptide linker sequences derived from known in vivo ERK targets, Ets1 and Elk1. Analysis of point mutations reveals specific residues involved in ERK binding and phosphorylation of ERK Activity Sensor 3. ERK2 also shows high in vitro specificity for these sensors over two other major MAP Kinases, p38 and pSAPK/JNK.</p><p><strong>Conclusion: </strong>EAS's are a convenient, non-radioactive alternative to study ERK dynamics in vitro. They can be utilized to study ERK activity in real-time. This new technology can be applied to studying ERK kinetics in vitro, analysis of ERK activity in whole cell extracts, and high-throughput screening technologies.</p>","PeriodicalId":80682,"journal":{"name":"BMC chemical biology","volume":"5 ","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2005-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6769-5-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24883073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An informatics search for the low-molecular weight chromium-binding peptide.","authors":"Deendayal Dinakarpandian,&nbsp;Vincent Morrissette,&nbsp;Shveta Chaudhary,&nbsp;Kambiz Amini,&nbsp;Brian Bennett,&nbsp;J David Van Horn","doi":"10.1186/1472-6769-4-2","DOIUrl":"https://doi.org/10.1186/1472-6769-4-2","url":null,"abstract":"<p><p>BACKGROUND: The amino acid composition of a low molecular weight chromium binding peptide (LMWCr), isolated from bovine liver, is reportedly E:G:C:D::4:2:2:2, though its sequence has not been discovered. There is some controversy surrounding the exact biochemical forms and the action of Cr(III) in biological systems; the topic has been the subject of many experimental reports and continues to be investigated. Clarification of Cr-protein interactions will further understanding Cr(III) biochemistry and provide a basis for novel therapies based on metallocomplexes or small molecules. RESULTS: A genomic search of the non-redundant database for all possible decapeptides of the reported composition yields three exact matches, EDGEECDCGE, DGEECDCGEE and CEGGCEEDDE. The first two sequences are found in ADAM 19 (A Disintegrin and Metalloproteinase domain 19) proteins in man and mouse; the last is found in a protein kinase in rice (Oryza sativa). A broader search for pentameric sequences (and assuming a disulfide dimer) corresponding to the stoichiometric ratio E:D:G:C::2:1:1:1, within the set of human proteins and the set of proteins in, or related to, the insulin signaling pathway, yields a match at an acidic region in the alpha-subunit of the insulin receptor (-EECGD-, residues 175-184). A synthetic peptide derived from this sequence binds chromium(III) and forms a metal-peptide complex that has properties matching those reported for isolated LMWCr and Cr(III)-containing peptide fractions. CONCLUSION: The search for an acidic decameric sequence indicates that LMWCr may not be a contiguous sequence. The identification of a distinct pentameric sequence in a significant insulin-signaling pathway protein suggests a possible identity for the LMWCr peptide. This identification clarifies directions for further investigation of LMWCr peptide fractions, chromium bio-coordination chemistry and a possible role in the insulin signaling pathway. Implications for models of chromium action in the insulin-signaling pathway are discussed.</p>","PeriodicalId":80682,"journal":{"name":"BMC chemical biology","volume":"4 1","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2004-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6769-4-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24863947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redesigned and chemically-modified hammerhead ribozymes with improved activity and serum stability.","authors":"Philip Hendry,&nbsp;Maxine J McCall,&nbsp;Tom S Stewart,&nbsp;Trevor J Lockett","doi":"10.1186/1472-6769-4-1","DOIUrl":"https://doi.org/10.1186/1472-6769-4-1","url":null,"abstract":"<p><p>BACKGROUND: Hammerhead ribozymes are RNA-based molecules which bind and cleave other RNAs specifically. As such they have potential as laboratory reagents, diagnostics and therapeutics. Despite having been extensively studied for 15 years or so, their wide application is hampered by their instability in biological media, and by the poor translation of cleavage studies on short substrates to long RNA molecules. This work describes a systematic study aimed at addressing these two issues. RESULTS: A series of hammerhead ribozyme derivatives, varying in their hybridising arm length and size of helix II, were tested in vitro for cleavage of RNA derived from the carbamoyl phosphate synthetase II gene of Plasmodium falciparum. Against a 550-nt transcript the most efficient (t1/2 = 26 seconds) was a miniribozyme with helix II reduced to a single G-C base pair and with twelve nucleotides in each hybridising arm. Miniribozymes of this general design were targeted to three further sites, and they demonstrated exceptional cleavage activity. A series of chemically modified derivatives was prepared and examined for cleavage activity and stability in human serum. One derivative showed a 103-fold increase in serum stability and a doubling in cleavage efficiency compared to the unmodified miniribozyme. A second was almost 104-fold more stable and only 7-fold less active than the unmodified parent. CONCLUSION: Hammerhead ribozyme derivatives in which helix II is reduced to a single G-C base pair cleave long RNA substrates very efficiently in vitro. Using commonly available phosphoramidites and reagents, two patterns of nucleotide substitution in this derivative were identified which conferred both good cleavage activity against long RNA targets and good stability in human serum.</p>","PeriodicalId":80682,"journal":{"name":"BMC chemical biology","volume":"4 1","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2004-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6769-4-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25022125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemical cleavage reactions of DNA on solid support: application in mutation detection.","authors":"Chinh T Bui, Andreana Lambrinakos, Jeffrey J Babon, Richard GH Cotton","doi":"10.1186/1472-6769-3-1","DOIUrl":"10.1186/1472-6769-3-1","url":null,"abstract":"<p><p>BACKGROUND: The conventional solution-phase Chemical Cleavage of Mismatch (CCM) method is time-consuming, as the protocol requires purification of DNA after each reaction step. This paper describes a new version of CCM to overcome this problem by immobilizing DNA on silica solid supports. RESULTS: DNA test samples were loaded on to silica beads and the DNA bound to the solid supports underwent chemical modification reactions with KMnO4 (potassium permanganate) and hydroxylamine in 3M TEAC (tetraethylammonium chloride) solution. The resulting modified DNA was then simultaneously cleaved by piperidine and removed from the solid supports to afford DNA fragments without the requirement of DNA purification between reaction steps. CONCLUSIONS: The new solid-phase version of CCM is a fast, cost-effective and sensitive method for detection of mismatches and mutations.</p>","PeriodicalId":80682,"journal":{"name":"BMC chemical biology","volume":"3 1","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2003-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC156887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22383618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and cytotoxicity of a biotinylated CC-1065 analogue.","authors":"Yuqiang Wang,&nbsp;Huiling Yuan,&nbsp;Susan C Wright,&nbsp;Hong Wang,&nbsp;James W Larrick","doi":"10.1186/1472-6769-2-1","DOIUrl":"10.1186/1472-6769-2-1","url":null,"abstract":"<p><p>BACKGROUND: The use of pretargeting technology for cancer imaging and treatment has made significant progress in the last few years. This approach takes advantage of the fact that biotin binds strongly to proteins avidin and streptavidin. Thus, a non-toxic tumor cell specific antibody is conjugated with avidin/streptavidin, and is administered to patients. After the antibody binds to tumor cells (usually 24--48 h); a clearing agent is given to remove the residual circulating antibodies in blood. Lastly, a toxic biotin-radioisotope conjugate is administered. Due to the small size of the biotin-radioisotope molecule and tight binding between biotin and avidin/streptavidin, the biotin-radioisotope rapidly binds to tumor cells with high specificity. CC-1065 (1) is one of a few classes of extremely potent antitumor agents, and a biotinalyted CBI-bearing CC-1065 analogue is a promising candidate to be used in the pretargeting technology to treat cancer. RESULTS: A biotinalyted CBI-bearing CC-1065 analogue, 6, was synthesized. The IC50 of 6 was 0.7 nM against U937 cells. Compound 6 caused apototsis of U937 cells. CONCLUSIONS: For the first time, a biotinalyted CBI-bearing CC-1065 analogue, 6, was synthesized. The biotinylated 6 can serve as a model compound to explore the usefulness of non-radioactive small molecule anticancer drugs in the pretargeting strategy for cancer imaging and therapy.</p>","PeriodicalId":80682,"journal":{"name":"BMC chemical biology","volume":"2 1","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6769-2-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65660554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Di-, tri- and tetra-5'-O-phosphorothioadenosyl substituted polyols as inhibitors of Fhit: Importance of the α-β bridging oxygen and β phosphorus replacement","authors":"J. Varnum, J. Baraniak, R. Kaczmarek, W. Stec, C. Brenner","doi":"10.1186/1472-6769-1-3","DOIUrl":"https://doi.org/10.1186/1472-6769-1-3","url":null,"abstract":"","PeriodicalId":80682,"journal":{"name":"BMC chemical biology","volume":"1 1","pages":"3 - 3"},"PeriodicalIF":0.0,"publicationDate":"2001-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6769-1-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65660495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of fluorescently labeled substance P analogs: binding, imaging and receptor activation","authors":"V. Bennett, M. A. Simmons","doi":"10.1186/1472-6769-1-1","DOIUrl":"https://doi.org/10.1186/1472-6769-1-1","url":null,"abstract":"","PeriodicalId":80682,"journal":{"name":"BMC chemical biology","volume":"1 1","pages":"1 - 1"},"PeriodicalIF":0.0,"publicationDate":"2001-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6769-1-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65660427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and preliminary cytotoxicity study of a cephalosporin-CC-1065 analogue prodrug.","authors":"Yuqiang Wang, Huiling Yuan, Susan C Wright, Hong Wang, James W Larrick","doi":"10.1186/1472-6769-1-4","DOIUrl":"10.1186/1472-6769-1-4","url":null,"abstract":"<p><p>BACKGROUND: Antibody-directed enzyme prodrug therapy (ADEPT) is a promising new approach to deliver anticancer drugs selectively to tumor cells. In this approach, an enzyme is conjugated to a tumor-specific antibody. The antibody selectively localizes the enzyme to the tumor cell surface. Subsequent administration of a prodrug substrate of the enzyme leads to the enzyme-catalyzed release of the free drug at the tumor site. The free drug will destroy the tumor cells selectively, thus, reducing side effects. RESULTS: A CC-1065 analogue was conjugated to a cephalosporin affording prodrug 2. The prodrug and its corresponding free drug, 1, have IC50 values of 0.9 and 0.09 nM, respectively, against U937 leukemia cells in vitro. CONCLUSIONS: For the first time, a prodrug comprised of a cephalosporin and a CC-1065 analogue has been synthesized. The preliminary in vitro studies show that the prodrug was 10-fold less toxic than the free drug. Prodrug 2 has the potential to be useful in cancer treatment using the ADEPT approach.</p>","PeriodicalId":80682,"journal":{"name":"BMC chemical biology","volume":"1 1","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC59845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65660545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calculated conformer energies for organic molecules with multiple polar functionalities are method dependent: Taxol (case study).","authors":"Ami Lakdawala, Minmin Wang, Neysa Nevins, Dennis C Liotta, Danuta Rusinska-Roszak, Marek Lozynski, James P Snyder","doi":"10.1186/1472-6769-1-2","DOIUrl":"10.1186/1472-6769-1-2","url":null,"abstract":"<p><p>BACKGROUND: Molecular mechanics (MM) and quantum chemical (QM) calculations are widely applied and powerful tools for the stereochemical and conformational investigations of molecules. The same methods have been extensively used to probe the conformational profile of Taxol (Figure 1) both in solution and at the beta-tubulin protein binding site. RESULTS: In the present work, the relative energies of seven conformations of Taxol derived from NMR and X-ray analyses were compared with a set of widely used force fields and semiempirical MO methods coupled to a continuum solvent treatment. The procedures not only diverge significantly in their assessment of relative conformational energies, but none of them provide satisfactory agreement with experiment. CONCLUSIONS: For Taxol, molecular mechanics and semiempirical QM methods are unable to provide a consistent energetic ranking of side-chain conformations. For similar highly polar organic structures, \"energy-free\" conformational search methods are advised.</p>","PeriodicalId":80682,"journal":{"name":"BMC chemical biology","volume":"1 1","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC59844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65660486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}