- β-Keto and β-hydroxyphosphonate analogs of biotin-5′-AMP are inhibitors of holocarboxylase synthetase
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Holocarboxylase synthetase (HLCS) catalyzes the covalent attachment of biotin to cytoplasmic and mitochondrial carboxylases, nuclear histones, and over a hundred human proteins. Nonhydrolyzable ketophosphonate (β-ketoP) and hydroxyphosphonate (β-hydroxyP) analogs of biotin-5′-AMP inhibit holocarboxylase synthetase (HLCS) with IC50 values of 39.7 μM and 203.7 μM. By comparison, an IC50 value of 7 μM was observed with the previously reported biotinol-5′-AMP. The Ki values, 3.4 μM and 17.3 μM, respectively, are consistent with the IC50 results, and close to the Ki obtained for biotinol-5′-AMP (7 μM). The β-ketoP and β-hydroxyP molecules are competitive inhibitors of HLCS while biotinol-5′-AMP inhibited HLCS by a mixed mechanism.
- Sittiwong, Wantanee,Cordonier, Elizabeth L.,Zempleni, Janos,Dussault, Patrick H.
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Read Online
- Expanding the substrate tolerance of biotin ligase through exploration of enzymes from diverse species
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Technologies that enable the site-specific conjugation of chemical probes onto proteins are extremely useful for applications in cell biology and proteomics. We cloned, expressed, and purified biotin ligases from nine different species and screened them for the ability to ligate unnatural analogues of biotin onto the human p67 biotin acceptor domain. We discovered that the biotin ligases of Saccharomyces cerevisiae (yeast) and Pyrococcus horikoshii could accept alkyne and azide derivatives of biotin, respectively. HPLC, gel-shift, and mass spectrometry assays confirmed that these ligation reactions were ATP- and enzyme-dependent, as well as site-specific. We used the P. horikoshii-catalyzed azide ligation reaction to site-specifically introduce a phosphine probe onto p67 using the Staudinger ligation. These new ligation reactions demonstrate the differential substrate specificities of biotin ligases from different organisms and open the door to novel protein labeling applications. Copyright
- Slavoff, Sarah A.,Chen, Irwin,Choi, Yoon-Aa,Ting, Alice Y.
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Read Online
- Design, synthesis, and biological evaluation of biotinylated colchicine derivatives as potential antitumor agents
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Chemical drug design based on the biochemical characteristics of cancer cells has become an important strategy for discovering new anti-tumour drugs to improve tumour targeting effects and reduce off-target toxicities. Colchicine is one of the most promin
- Wang, Chao,Zhang, Yujing,Wang, Zeyu,Li, Yuelin,Guan, Qi,Xing, Dongming,Zhang, Weige
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p. 411 - 420
(2021/12/24)
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- BIOPROBES FOR LYSYL OXIDASES AND USES THEREOF
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The present invention relates to novel bioprobes which are capable of binding to certain amine oxidase enzymes. These bioprobes are useful in methods of detecting and determining the concentration of certain amine oxidase enzymes in a sample as well as in methods for the quantitative assessment of inhibition of certain amine oxidases.
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Paragraph 00185
(2021/08/14)
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- Azoacetylenes for the Synthesis of Arylazotriazole Photoswitches
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We report a modular approach toward novel arylazotriazole photoswitches and their photophysical characterization. Addition of lithiated TIPS-acetylene to aryldiazonium tetrafluoroborate salts gives a wide range of azoacetylenes, constituting an underexplored class of stable intermediates.In situdesilylation transiently leads to terminal arylazoacetylenes that undergo copper-catalyzed cycloadditions (CuAAC) with a diverse collection of organoazides. These include complex molecules derived from natural products or drugs, such as colchicine, taxol, tamiflu, and arachidonic acid. The arylazotriazoles display near-quantitative photoisomerization and long thermalZ-half-lives. Using the method, we introduce for the first time the design and synthesis of a diacetylene platform. It permits implementation of consecutive and diversity-oriented approaches linking two different conjugants to independently addressable acetylenes within a common photoswitchable azotriazole. This is showcased in the synthesis of several photoswitchable conjugates, with potential applications as photoPROTACs and biotin conjugates.
- Anderl, Felix,Balkenhohl, Moritz,Carreira, Erick M.,Fink, Moritz,Pfaff, Patrick
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supporting information
p. 14495 - 14501
(2021/09/18)
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- Site-Selective Modification of Peptides and Proteins via Interception of Free-Radical-Mediated Dechalcogenation
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The development of site-selective chemistry targeting the canonical amino acids enables the controlled installation of desired functionalities into native peptides and proteins. Such techniques facilitate the development of polypeptide conjugates to advance therapeutics, diagnostics, and fundamental science. We report a versatile and selective method to functionalize peptides and proteins through free-radical-mediated dechalcogenation. By exploiting phosphine-induced homolysis of the C?Se and C?S bonds of selenocysteine and cysteine, respectively, we demonstrate the site-selective installation of groups appended to a persistent radical trap. The reaction is rapid, operationally simple, and chemoselective. The resulting aminooxy linker is stable under a variety of conditions and selectively cleavable in the presence of a low-oxidation-state transition metal. We have explored the full scope of this reaction using complex peptide systems and a recombinantly expressed protein.
- Griffiths, Rhys C.,Smith, Frances R.,Long, Jed E.,Williams, Huw E. L.,Layfield, Robert,Mitchell, Nicholas J.
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supporting information
p. 23659 - 23667
(2020/10/21)
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- LIGAND LINKER SUBSTRATE
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Ligand functionalized substrate including a solid substrate, which has been modified to provide grafted catching ligand groups covalently bound via a linker, methods of preparing said ligand functionalized substrate and the use thereof, such as to increase binding rate and the dynamic binding capacity (DBC).
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Page/Page column 11
(2020/07/15)
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- SYNTHETIC RECEPTORS FOR IONOPHORIC COMPOUNDS
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The present invention relates to synthetic receptors for ionophoric compounds, such as ionophoric toxins. Hence, the invention provides synthetic molecules capable of binding different ionophoric compounds, thereby being suitable for use in the detection,
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Page/Page column 35
(2019/09/18)
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- Design and synthesis of biotinylated cardiac glycosides for probing Nur77 protein inducting pathway
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The orphan nuclear receptor Nur77 (also known as TR3 or nerve growth factor-induced clone B NGFI-B) functions as a nuclear transcription factor in the regulation of target gene expression and plays a critical role in the regulation of differentiation, proliferation, apoptosis, and survival of many different cell types. Recent studies demonstrate that Nur77 also involves many important physiological and pathological processes including cancer, inflammation and immunity, cardiovascular diseases, and bone diseases. Our previous studies showed that cardiac glycosides could induce the expression of Nur77 protein and its translocation from the nucleus to the cytoplasm and subsequent targeting to mitochondria, leading to apoptosis of cancer cells. In order to probe the Nur77 protein inducting pathway, we designed and synthesized a series of novel biotinylated cardiac glycosides from β-Antiarin and α-Antiarin, two typical cardiac glycosides from the plant of Antiaris toxicaria. The induction of Nur77 protein expression of these biotinylated cardiac glycosides and their inhibitory effects on NIH-H460 cancer cell proliferation were evaluated. Results displayed that some biotinylated cardiac glycosides could significantly induce the expression of Nur77 protein comparable with their parent compounds β-Antiarin and α-Antiarin. Also, their streptavidin binding activities were evaluated. Among them, biotinylated cardiac glycosides P4b and P5a exhibited significant effect on the induction of Nur77 expression along with high binding capacity with streptavidin, suggesting that they can be used as probes for probing Nur77 protein inducting pathway.
- Tian, Dan-mei,Qiao, Jia,Bao, Yu-zhou,Liu, Jie,Zhang, Xiao-kun,Sun, Xue-long,Zhang, You-wei,Yao, Xin-sheng,Tang, Jin-shan
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supporting information
p. 707 - 712
(2019/01/22)
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- Chemoselective triazole-phosphonamidate conjugates suitable for photorelease
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Herein, we describe a new method for the conjugation of azide-containing target compounds that can be readily released as amines by irradiation with near UV light. This concept is based on a two-step protocol employing the chemoselective CuAAC and Staudinger-phosphonite reactions to deliver photo-cleavable phosphonamidate conjugates in high yields starting from 2-nitrobenzyl substituted phosphonites.
- Siebertz, Kristina D.,Hackenberger, Christian P. R.
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supporting information
p. 763 - 766
(2018/02/06)
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- Rapid Characterization of a Mechanically Labile α-Helical Protein Enabled by Efficient Site-Specific Bioconjugation
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Atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) is a powerful yet accessible means to characterize mechanical properties of biomolecules. Historically, accessibility relies upon the nonspecific adhesion of biomolecules to a surface and a cantilever and, for proteins, the integration of the target protein into a polyprotein. However, this assay results in a low yield of high-quality data, defined as the complete unfolding of the polyprotein. Additionally, nonspecific surface adhesion hinders studies of α-helical proteins, which unfold at low forces and low extensions. Here, we overcame these limitations by merging two developments: (i) a polyprotein with versatile, genetically encoded short peptide tags functionalized via a mechanically robust Hydrazino-Pictet-Spengler ligation and (ii) the efficient site-specific conjugation of biomolecules to PEG-coated surfaces. Heterobifunctional anchoring of this polyprotein construct and DNA via copper-free click chemistry to PEG-coated substrates and a strong but reversible streptavidin-biotin linkage to PEG-coated AFM tips enhanced data quality and throughput. For example, we achieved a 75-fold increase in the yield of high-quality data and repeatedly probed the same individual polyprotein to deduce its dynamic force spectrum in just 2 h. The broader utility of this polyprotein was demonstrated by measuring three diverse target proteins: an α-helical protein (calmodulin), a protein with internal cysteines (rubredoxin), and a computationally designed three-helix bundle (α3D). Indeed, at low loading rates, α3D represents the most mechanically labile protein yet characterized by AFM. Such efficient SMFS studies on a commercial AFM enable the rapid characterization of macromolecular folding over a broader range of proteins and a wider array of experimental conditions (pH, temperature, denaturants). Further, by integrating these enhancements with optical traps, we demonstrate how efficient bioconjugation to otherwise nonstick surfaces can benefit diverse single-molecule studies.
- Walder, Robert,Leblanc, Marc-André,Van Patten, William J.,Edwards, Devin T.,Greenberg, Jacob A.,Adhikari, Ayush,Okoniewski, Stephen R.,Sullan, Ruby May A.,Rabuka, David,Sousa, Marcelo C.,Perkins, Thomas T.
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supporting information
p. 9867 - 9875
(2017/08/02)
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- A versatile platform for adding functional properties to amyloid fibrils
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Herein we report the design, synthesis, and testing of prototype members of a family of amyloid-binding molecular tools that can manipulate the fibrils by giving them various new functional properties. Potential applications include manipulating disease-r
- Fontaine, Devon F. A.,Ivancic, Valerie A.,Reardon, Michael B.,Lazo, Noel D.,Jakobsche, Charles E.
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supporting information
p. 8023 - 8027
(2017/10/10)
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- Structural Analysis of Substrate, Reaction Intermediate, and Product Binding in Haemophilus influenzae Biotin Carboxylase
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Acetyl-CoA carboxylase catalyzes the first and regulated step in fatty acid synthesis. In most Gram-negative and Gram-positive bacteria, the enzyme is composed of three proteins: biotin carboxylase, a biotin carboxyl carrier protein (BCCP), and carboxyltransferase. The reaction mechanism involves two half-reactions with biotin carboxylase catalyzing the ATP-dependent carboxylation of biotin-BCCP in the first reaction. In the second reaction, carboxyltransferase catalyzes the transfer of the carboxyl group from biotin-BCCP to acetyl-CoA to form malonyl-CoA. In this report, high-resolution crystal structures of biotin carboxylase from Haemophilus influenzae were determined with bicarbonate, the ATP analogue AMPPCP; the carboxyphosphate intermediate analogues, phosphonoacetamide and phosphonoformate; the products ADP and phosphate; and the carboxybiotin analogue N1′-methoxycarbonyl biotin methyl ester. The structures have a common theme in that bicarbonate, phosphate, and the methyl ester of the carboxyl group of N1′-methoxycarbonyl biotin methyl ester all bound in the same pocket in the active site of biotin carboxylase and as such utilize the same set of amino acids for binding. This finding suggests a catalytic mechanism for biotin carboxylase in which the binding pocket that binds tetrahedral phosphate also accommodates and stabilizes a tetrahedral dianionic transition state resulting from direct transfer of CO2 from the carboxyphosphate intermediate to biotin.
- Broussard, Tyler C.,Pakhomova, Svetlana,Neau, David B.,Bonnot, Ross,Waldrop, Grover L.
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p. 3860 - 3870
(2015/06/30)
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- Improved synthesis of biotinol-5′-AMP: Implications for antibacterial discovery
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An improved synthesis of biotinol-5′-AMP, an acyl-AMP mimic of the natural reaction intermediate of biotin protein ligase (BPL), is reported. This compound was shown to be a pan inhibitor of BPLs from a series of clinically important bacteria, particularl
- Tieu, William,Polyak, Steven W.,Paparella, Ashleigh S.,Yap, Min Y.,Soares Da Costa, Tatiana P.,Ng, Belinda,Wang, Geqing,Lumb, Richard,Bell, Jan M.,Turnidge, John D.,Wilce, Matthew C. J.,Booker, Grant W.,Abell, Andrew D.
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p. 216 - 220
(2015/03/04)
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- KAHA ligations that form aspartyl aldehyde residues as synthetic handles for protein modification and purification
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Aldehydes are widely recognized as valuable synthetic handles for the chemoselective manipulation of peptides and proteins. In this report, we show that peptides and small proteins containing the aspartic acid semialdehyde (Asa) side chain can be easily p
- Murar, Claudia E.,Thuaud, Frdric,Bode, Jeffrey W.
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supporting information
p. 18140 - 18148
(2015/03/04)
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- BIOTINIDASE RESISTANT BIOTINYL COMPOUNDS
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Disclosed are biotinidase resistant biotinyl-conjugates, and uses thereof. The conjugates comprise a biotinyl moiety coupled to a therapeutic or diagnostic moiety by a triazole group. The conjugates have applications as diagnostic or therapeutic agents, in methods of diagnosis or treatment of a subject, for example as MRI contrast agents in MRI imaging of a subject. In particular, biotinyl-chelate complexes find utility in two and three step pretargeting strategies and have high affinity for avidin, streptavidin and related proteins. Also disclosed are biotinylating agents and kits, and the use of compounds for biotinylation, including for the synthesis of biotinyl-chelate complexes and biotinyl-conjugates.
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Page/Page column 39; 40
(2013/10/21)
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- Biotin analogues with antibacterial activity are potent inhibitors of biotin protein ligase
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There is a desperate need to develop new antibiotic agents to combat the rise of drug-resistant bacteria, such as clinically important Staphylococcus aureus. The essential multifunctional enzyme, biotin protein ligase (BPL), is one potential drug target f
- Soares Da Costa, Tatiana P.,Tieu, William,Yap, Min Y.,Zvarec, Ondrej,Bell, Jan M.,Turnidge, John D.,Wallace, John C.,Booker, Grant W.,Wilce, Matthew C. J.,Abell, Andrew D.,Polyak, Steven W.
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scheme or table
p. 509 - 514
(2012/08/14)
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- Design of a reversible biotin analog and applications in protein labeling, detection, and isolation
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To expand the applicability of the biotin-(strept)avidin system, a biotin analog with reversible binding under non-denaturing conditions has been designed, and its applications in protein labeling, detection, and isolation have been evaluated. The Royal S
- Ying, Lai-Qiang,Branchaud, Bruce P.
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supporting information; experimental part
p. 8593 - 8595
(2011/09/15)
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- A photocleavable rapamycin conjugate for spatiotemporal control of small GTPase activity
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We developed a novel method to spatiotemporally control the activity of signaling molecules. A newly synthesized photocaged rapamycin derivative induced rapid dimerization of FKBP (FK-506 binding protein) and FRB (FKBP-rapamycin binding protein) upon UV i
- Umeda, Nobuhiro,Ueno, Tasuku,Pohlmeyer, Christopher,Nagano, Tetsuo,Inoue, Takanari
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supporting information; scheme or table
p. 12 - 14
(2011/03/17)
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- Selective N-acylation and N-alkylation of biotin
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Simple and efficient methodology is presented for the selective acylation and alkylation of biotin at its 3′-nitrogen.
- Pehere, Ashok D.,Abell, Andrew D.
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scheme or table
p. 9514 - 9518
(2012/01/06)
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- BIOMOLECULAR LABELLING USING MULTIFUNCTIONAL BIOTIN ANALOGUES
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Novel biotin analogues, such as 2-Azidobiotin, comprising the ureido ring of natural biotin with the thiophene ring, optionally modified, and a modified sidechain having a functional end group, preferably selected from the group consisting of a carboxylic
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Page/Page column 27-28
(2010/10/03)
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- Bismuth(III) triflate: A safe and easily handled precursor for triflic acid: Application to the esterification reaction
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A series of carboxylic acids were converted into their corresponding methyl esters using bismuth(III) triflate as a catalyst in methanol. Good to excellent yields were obtained for different aliphatic or aromatic starting materials. In the reaction, bismuth triflate acts as a precursor that, upon hydrolysis, liberates sufficient triflic acid to catalyze the esterification.
- Kwie, Franciane Ho A.,Baudoin-Dehoux, Cecile,Blonski, Casimir,Lherbet, Christian
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experimental part
p. 1082 - 1087
(2010/05/01)
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- Molecular recognition studies on naphthyridine derivatives
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The association constants Kb of three hosts I-III designed to have both enhanced hydrogen bonding donor strength and conformational preorganization with biotin analogues 1-5 are reported. 1H-NMR titrations under two different concent
- Iglesias-Sanchez, Jose Carlos,Maria, Dolores Santa,Claramunt, Rosa M.,Elguero, Jose
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experimental part
p. 1213 - 1222
(2010/06/15)
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- Ditryptophan conjugation triggers conversion of biotin fibers into soft spherical structures
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(Figure Presented) Trigger happy: Biotin and its methyl ester form long fibers in solution, which are transformed into soft spherical structures upon simple conjugation with ditryptophan dipeptide (see picture). Such morphogenesis is not achieved in a controlled fashion by other aromatic amino acids.
- Joshi,Verma, Sandeep
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supporting information; experimental part
p. 2860 - 2863
(2009/02/06)
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- Bioconjugation of biotinylated PAMAM dendrons to avidin
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The biotin-terminated PAMAM dendron has been synthesized and the asymmetric dendron used to modify the protein avidin via non-covalent bioconjugation. The Royal Society of Chemistry.
- Tao, Lei,Geng, Jin,Chen, Gaojian,Xu, Yingjian,Ladmiral, Vincent,Mantovani, Giuseppe,Haddleton, David. M.
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p. 3441 - 3443
(2008/03/12)
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- Synthesis of the ribosomal P-site substrate CCA-pcb
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(Chemical Equation Presented) CCA-pcb (cytidylyl-(3′5′)- cytidylyl-(3′5′)-3′(2′)-O-(N-(6-D-(+) -biotinoylaminohexanoyl)-L-phenylalanyl)adenosine), a ribosomal P-site substrate, was synthesized by phosphoramidite chemistry in 26 steps with an overall yield
- Zhong, Minghong,Strobel, Scott A.
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- A highly stereocontrolled total synthesis of (+)-biotin from L-cysteine
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(+)-Biotin was synthesized in 11 steps and in 25% overall yield from readily accessible L-cysteine through a Lewis base-catalyzed highly diastereoselective cyanosilylation of (2R,4R)-N-Boc-2-phenylthiazolidine-4-carbaldehyde 2 and a ring closure of a cis-allylic carbonate 5b utilizing a palladium-catalyzed intramolecular allylic amination.
- Seki, Masahiko,Hatsuda, Masanori,Mori, Yoshikazu,Yamada, Shin-Ichi
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p. 3269 - 3272
(2007/10/03)
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- Theoretical and experimental studies of biotin analogues that bind almost as tightly to streptavidin as biotin
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We have used a newly developed qualitative computational approach, PROFEC (Pictorial Representation of Free Energy Changes), to visualize the areas of the ligand biotin where modifications of its structure might lead to tighter binding to the protein streptavidin. The PROFEC analysis, which includes protein flexibility and ligand sotvation/desolvation, led to the suggestion that the pro-9R hydrogen atom of biotin, which is in α-position to the CO2- group, might be changed to a larger group and lead to better binding with streptavidin and avidin. Free energy calculations supported this suggestion and predicted that the methyl analogue should bind ≈3 kcal/mol more tightly to streptavidin, with this difference coming exclusively from the relative desolvation free energy of the ligand. The PROFEC analysis further suggested little or no improvement for changing the pro-9S hydrogen atom to a methyl group, and great reduction in changing the ureido N-H groups to N-CH3. Stimulated by these results, we synthesized 9R-methylbiotin and 9S-methylbiotin, and their binding free energies and enthalpies were measured for interaction with streptavidin and avidin, respectively. In contrast to the calculated results, experiments found both 9-methylbiotin isomers to bind more weakly to streptavidin than biotin. The calculated preference for the binding of the 9R- over the 9S-stereoisomer was observed. In addition, 9-methylbiotin is considerably less soluble in water than biotin, as predicted by the calculation, and the 9R isomer is, to our knowledge, thus far the tightest binding analogue of biotin to streptavidin. Subsequently, X-ray structures of the complexes between streptavidin and both 9R- and 9S-methylbiotin were determined, and the structures were consistent with those used in the free energy calculations. Thus, the reason for the discrepancy between the calculated and experimental binding free energy does not lie in unusual binding modes for the 9-methylbiotins.
- Dixon, Richard W.,Radmer, Randall J.,Kuhn, Bernd,Kollman, Peter A.,Yang, Jaemoon,Raposo, Cesar,Wilcox, Craig S.,Klumb, Lisa A.,Stayton, Patrick S.,Behnke, Craig,Le Trong, Isolde,Stenkamp, Ronald
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p. 1827 - 1837
(2007/10/03)
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- Preparation and biological properties of biotinylated PhTX derivatives
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We report the synthesis of several highly functionalized biotinylated philanthotoxin (PhTX) analogues (7, 8, 10, 13-16) designed on the basis of earlier structure-activity relationship studies. Despite the extensive modifications, the binding to nicotinic acetylcholine receptor (nAChR) is in the low micromolar range according to an inhibition assay using 3H-thienylcyclohexyl-piperidine (TCP). A patch clamp functional assay gave comparable results. Compounds exemplified by 16, which consists of a biotinylated ligand linked to a bifunctional photoaffinity probe (BPP), represent a new type of probe which should find use in photo-cross-linking studies of ligand-receptor interactions. Copyright (C) 1999 Elsevier Science Ltd.
- Hashimoto, Masaru,Liu, Ying,Fang, Kan,Li, Hong-Yu,Campiani, Giuseppe,Nakanishi, Koji
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p. 1181 - 1194
(2007/10/03)
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- Synthesis of (+)-biotin derivatives as HIV-1 protease inhibitors
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Several bis-N-alkylated (+)-biotin derivatives were synthesized and evaluated for activities against HIV-1 protease. The most potent inhibitor, 2D, synthesized in two steps from (+)-biotin, has K(i) of 0.50 μM and antiviral IC90 of 7 μM. The (+
- Han, Qi,Lafontaine, Jennifer,Bacheler, Lee T.,Rayner, Marlene M.,Klabe, Ronald M.,Erickson-Viitanen, Susan,Lam, Patrick Y.S.
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p. 1371 - 1374
(2007/10/03)
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- Spatially-addressable immobilization of macromolecules on solid supports
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A method is described for immobilization of receptors, antibodies, or other macromolecules at precise locations on solid substrates. We have combined photolithographic techniques with the use of a 'caged' biotin analogue that has been covalently linked to
- Sundberg, Steven A.,Barrett, Ronald W.,Pirrung, Michael,Lu, Amy L.,Kiangsoontra, Benjang,Holmes, Christopher P.
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p. 12050 - 12057
(2007/10/03)
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- REACTION OF XeF2. PART 7. SYNTHESIS OF 6-FLUOROBIOTIN METHYL ESTER
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The synthesis of 6-fluoro-d-biotin methyl ester and its characterization by (1)H and (19)F nmr and elemental analysis is described.Analogous reactions of XeF2 with tetramisole and benzylpenicillin methyl ester were carried out but monofluorinated products
- Huang, Xiaoling,Blackburn, Barry J.,Janzen, Alexander F.
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p. 145 - 150
(2007/10/02)
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- Chemistry of Biotin: Access to 2,3- and 5,6-Didehydrobiotin Derivatives
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Dehydration of the N1'-acetylbiotin methyl ester sulphoxides (3a) and (3b) under a variety of conditions affords the didehydrobiotin derivatives (4) and (5a). 5,6-Didehydrobiotin (5b) is effective as a biotin replacement factor for a bioA mutant of E. coli.
- Baxter, Robert L.,Coutts, Andrew
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p. 913 - 916
(2007/10/02)
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- Process for the preparation of biotin
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A novel process is described for preparation of biotin comprising preparation of substituted 3H, 5H-imidazo[1, 5c]tetrahydro thiazoles by contacting the boron trifluoride adduct of an appropriate thiazoline with the metallic derivative of an ester enolate, reducing the ester, hydrolyzing the thiazolidine moiety and hydrolyzing or oxidizing the resultant compound. Intermediates obtained in the preparation of biotin by the above process and alternate procedures for preparing said intermediates are also presented. A novel process for preparation of d-biotin is also given.
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- A total synthesis of (+/-)-biotin
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A total synthesis of (+/-)-biotin 1 based on the photochemical cycloaddition raection of 1,3-diacetylimidazolin-2-one 2 with 3,4-dihydro-2-methoxy-2H-pyran 3 is described.The photoadduct 4 was converted into the lactone 6, which bears the complete carbon framework and all the requisite stereochemical features, via hydrolysis, Wittig olefination, and catalytic hydrogenation to the cyclobutanol 5 followed by oxidative rearrangement.Subsequent conversion of the lactone to (+/-)-biotin followed from literature precedent (5).
- Whitney, Ralph Allen
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p. 1158 - 1160
(2007/10/02)
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- SYNTHESIS OF (+-)-BIOTIN FROM A SUBSTITUTED 2,3-DEHYDROTHIOPHANE
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(+-)-Biotin has been synthesized from a mixture of cis- and allo-trisubstituted dehydrothiophanes by a scheme providing for the easy elimination of the accompanying allo-substituted thiophane in the form of an intermediate and not as the final isomeric allo-biotin.The imidazoline ring of biotin is formed from a dialkoxycarbonyldiaminothiophane under the conditions of partial hydrolysis of one of the protective groups with the elimination of phosgene from the scheme of synthesis.
- Mikhano, S. D.,Kulachkina, N. S.,Filippova, T. M.,Suchkova, I. G.,Berezovskii, V. M.
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p. 176 - 178
(2007/10/02)
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- Olefinic Nitrone and Nitrile Oxide Cycloadditions. A Short Stereospecific Synthesis of Biotin from Cycloheptene
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A novel synthesis of biotine (6) from cycloheptene (4) via the key amino alcohol 5 is described.The synthetic scheme is based upon an intramolecular nitrone-olefin cycloaddition of the reactive intermediate 13, generated in situ from the aldehyde
- Confalone, Pat N.,Pizzolato, Giacomo,Confalone, Dianne Lollar,Uskokovic Milan R.
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p. 1954 - 1960
(2007/10/02)
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- Synthesis of biotin
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Synthesis of biotin from 4-carbomethoxy-2-(4,5-dihydrothiophen-3(2H)-one)-valeric acid methyl ester, and thiophene intermediates in this synthesis.
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