- Modulating Angiogenesis by Proteomimetics of Vascular Endothelial Growth Factor
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Angiogenesis, formation of new blood vessels from the existing vascular network, is a hallmark of cancer cells that leads to tumor vascular proliferation and metastasis. This process is mediated through the binding interaction of VEGF-A with VEGF receptor
- Abdulkadir, Sami,Cai, Jianfeng,Hu, Yong,Jiang, Wei,Li, Chunpu,Li, Qi,Sang, Peng,Wei, Lulu,Zhao, Xue
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supporting information
p. 270 - 281
(2022/01/19)
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- PNA probe
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Disclosed herein are improved PNA based monomers, nucleobases, oligomers and probes for use in a variety of different methods of analysing nucleic acids. Further, the disclosure provides methods of preparing the modified and improved PNA molecules as well as methods of using the same.
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Paragraph 0279; 0283
(2022/02/16)
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- Β?CATENIN/ B-CELL LYMPHOMA 9 PROTEIN?PROTEIN INTERACTION INHIBITING PEPTIDOMIMETICS
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Disclosed herein is a series of helical sulfono-γ-AApeptides that mimic the binding mode of the α-helical HD2 domain of B-Cell Lymphoma 9 (BCL9). As disclosed herein, sulfono-γ-AApeptides can structurally and functionally mimic the α-helical domain of BCL9, and selectively disrupt β?catenin/BCL9 PPIs with even higher potency. More intriguingly, these sulfono-γ-AApeptides can enter cancer cells, bind with β?catenin and disrupt β?catenin/BCL PPI, and exhibit excellent cellular activity, which is much more potent than the BCL9 peptide. Furthermore, enzymatic stability studies demonstrated the remarkable stability of the helical sulfono-γ-AApeptides, with no degradation in the presence of pronase for 24 h, augmenting their biological potential.
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Paragraph 0167
(2020/11/03)
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- α-Helix-Mimicking Sulfono-γ-AApeptide Inhibitors for p53-MDM2/MDMX Protein-Protein Interactions
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The use of peptidomimetic scaffolds is a promising strategy for the inhibition of protein-protein interactions (PPIs). Herein, we demonstrate that sulfono-γ-AApeptides can be rationally designed to mimic the p53 α-helix and inhibit p53-MDM2 PPIs. The best
- Sang, Peng,Shi, Yan,Lu, Junhao,Chen, Lihong,Yang, Leixiang,Borcherds, Wade,Abdulkadir, Sami,Li, Qi,Daughdrill, Gary,Chen, Jiandong,Cai, Jianfeng
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p. 975 - 986
(2020/03/10)
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- Design and synthesis of irreversible inhibitors of foot-and-mouth disease virus 3C protease
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Foot-and-mouth disease virus (FMDV) causes a highly infectious and economically devastating disease of livestock. The FMDV genome is translated as a single polypeptide precursor that is cleaved into functional proteins predominantly by the highly conserve
- Roque Rosell, Nuria R.,Mokhlesi, Ladan,Milton, Nicholas E.,Sweeney, Trevor R.,Zunszain, Patricia A.,Curry, Stephen,Leatherbarrow, Robin J.
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p. 490 - 494
(2014/01/23)
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- Comparison of backbone modification in protein β-sheets by α→γ residue replacement and α-residue methylation
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The mimicry of protein tertiary structure by oligomers with unnatural backbones is a significant contemporary research challenge. Among common elements of secondary structure found in natural proteins, sheets have proven the most difficult to address. Here, we report the systematic comparison of different strategies for peptide backbone modification in β-sheets with the goal of identifying the best method for replacing a multi-stranded sheet in a protein tertiary fold. The most effective sheet modifications examined led to native-like tertiary folding behavior with a thermodynamic folded stability comparable to the prototype protein on which the modified backbones are based. This journal is the Partner Organisations 2014.
- Lengyel, George A.,Reinert, Zachary E.,Griffith, Brian D.,Horne, W. Seth
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supporting information
p. 5375 - 5381
(2014/07/21)
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- N-Acylpolyamine inhibitors of HDM2 and HDMX binding to p53
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Selective inhibition of protein-protein interactions important for cellular processes could lead to the development of new therapies against disease. In the area of cancer, overexpression of the proteins human double minute 2 (HDM2) and its homolog HDMX has been linked to tumor aggressiveness. Both HDM2 and HDMX bind to p53 and prevent cell cycle arrest or apoptosis in damaged cells. Developing a strategy to simultaneously prevent the binding of both HDM2 and HDMX to p53 is an essential feature of inhibitors to restore p53 activity in a number of different cancers. Inhibition of protein-protein interactions with synthetic molecules is an emerging area of research that requires new inhibitors tailored to mimic the types of interfaces between proteins. Our strategy to create inhibitors of protein-protein interactions is to develop a non-natural scaffold that may be used as a starting point to identify important molecular components necessary for inhibition. In this study, we report an N-acylpolyamine (NAPA) scaffold that supports numerous sidechains in a compact atomic arrangement. NAPAs were constructed by a series of reductive aminations between amino acid derivatives followed by acylation at the resulting secondary amine. An optimized NAPA was able to equally inhibit the association of both HDM2 and HDMX with p53. Our results demonstrate some of the challenges associated with targeting multiple protein-protein interactions involved in overlapping cellular processes.
- Hayashi, Ryo,Wang, Deyun,Hara, Toshiaki,Iera, Jaclyn A.,Durell, Stewart R.,Appella, Daniel H.
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supporting information; experimental part
p. 7884 - 7893
(2010/03/30)
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- DMSO-aided o-iodoxybenzoic acid (IBX) oxidation of Fmoc-protected amino alcohols
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A fast and highly convenient procedure for the formation of Fmoc-protected amino aldehydes from the corresponding alcohols using 1.1 equiv. of IBX in the presence of dimethylsulfoxide (DMSO) is discussed. This procedure leads to the clean synthesis of Fmo
- Chen, Jack J.,Aduda, Vince
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p. 3493 - 3499
(2008/03/13)
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- Melanocortin receptor-specific compounds
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A melanocortin receptor-specific compound of the general formula of structure I: where X, R1, R2a, R2b, R3, R4a, R4b, R5a and R5b are as defined in the specification,
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- Isoxazoline derivative and a process for the preparation thereof
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The present invention provides to an isoxazoline derivative of formula (I), the pharmaceutically acceptable salts, esters and stereochemically isomeric forms thereof, and the use of the derivative in inhibiting the activity of caspases. The present invent
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Page/Page column 38
(2010/02/07)
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- Solid-phase synthesis of peptide vinyl sulfones as potential inhibitors and activity-based probes of cysteine proteases
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(Matrix presented) Peptide vinyl sulfones were prepared from 2-chlorotrityl resin-bound phenolic amino vinyl sulfones in high yield and purity. This method enables the convenient synthesis of peptide vinyl sulfones having different amino acids at the Psu
- Wang, Gang,Mahesh, Uttamchandani,Chen, Grace Y. J.,Yao, Shao Q.
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p. 737 - 740
(2007/10/03)
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- A novel, one-pot reductive alkylation of amines by S-ethyl thioesters mediated by triethylsilane and sodium triacetoxyborohydride in the presence of palladium on carbon
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The reductive alkylation of primary amines with aldehydes or ketones is an important tool in the synthesis of wide variety of amines. We described here a novel, one-pot reductive alkylation method using multifunctional S- ethyl thioesters as a source for
- Han, Yinglin,Chorev, Michael
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p. 1972 - 1978
(2007/10/03)
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- Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 2. Peptide structure- activity studies
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The structure-based design, chemical synthesis, and biological evaluation of various peptidederived human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. These compounds are comprised of an ethyl propenoate Michael acceptor moiety and a tripeptidyl binding determinant. The systematic modification of each amino acid residue present in the binding determinant as well as the N-terminal functionality is described. Such modifications are shown to provide irreversible HRV-14 3CP inhibitors with anti-3CP activities (k(obs)/[I]) ranging from 60 to 280 000 M-1 s-1 and antiviral EC50's which approach 0.15 μM. An optimized inhibitor which incorporates several improvements identified by the structure-activity studies is also described. This molecule displays very rapid irreversible inhibition of HRV-14 3CP (k(obs)/[I] = 800 000 M-1 s-1) and potent antiviral activity against HRV-14 in cell culture (EC50 = 0.056 μM). A 1.9 A? crystal structure of an S-alkylthiocarbamate-containing inhibitor complexed with HRV-2 3CP is also detailed.
- Dragovich, Peter S.,Webber, Stephen E.,Babine, Robert E.,Fuhrman, Sheila A.,Patick, Amy K.,Matthews, David A.,Reich, Siegfried H.,Marakovits, Joseph T.,Prins, Thomas J.,Zhou, Ru,Tikhe, Jayashree,Littlefield, Ethel S.,Bleckman, Ted M.,Wallace, Michael B.,Little, Thomas L.,Ford, Clifford E.,Meador III, James W.,Ferre, Rose Ann,Brown, Edward L.,Binford, Susan L.,DeLisle, Dorothy M.,Worland, Stephen T.
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p. 2819 - 2834
(2007/10/03)
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