- MACROCYCLIC THERAPEUTIC AGENTS, METHODS OF MANUFACTURE, AND METHODS OF TREATMENT
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The instant invention describes macrocyclic compounds having therapeutic activity, and the mechanism and methods of treating disorders such as autoimmune diseases, inflammation, and cancer, tumors and cell proliferation related disorders.
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Page/Page column 75; 76; 78
(2015/09/28)
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- Improved total synthesis and biological evaluation of potent apratoxin S4 based anticancer agents with differential stability and further enhanced activity
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Apratoxins are cytotoxic natural products originally isolated from marine cyanobacteria that act by preventing cotranslational translocation early in the secretory pathway to downregulate receptor levels and inhibit growth factor secretion, leading to pot
- Chen, Qi-Yin,Liu, Yanxia,Cai, Weijing,Luesch, Hendrik
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supporting information
p. 3011 - 3029
(2014/05/06)
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- Convergent synthesis of peptide nucleic acids by native chemical ligation
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(Chemical Equation Presented) A convergent strategy for synthesizing long contiguous PNA by a native chemical ligation-like technique of PNA segment couplings is presented. This approach required the synthesis of a new PNA-monomer featuring a 1-amino-2-th
- Dose, Christian,Seitz, Oliver
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p. 4365 - 4368
(2007/10/03)
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- Design and synthesis of non-peptide Ras CAAX mimetics as potent farnesyltransferase inhibitors
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Cysteine farnesylation of the ras oncogene product Ras is required for its transforming activity and is catalyzed by farnesyltransferase (FTase). The Ras carboxyl terminal tetrapeptide CAAX (C is cysteine, A is any aliphatic amino acid, X is methionine or serine) is the minimum sequence for FTase recognition. We report here the design, synthesis, and biological characterization of Ras CAAX non-peptide mimetics in which the cysteine is linked through a reduced pseudopeptide bond to 4-amino-3'-carboxybiphenyl. These non-peptide mimetics are potent inhibitors of FTase (IC50 = 40 nM for the most potent inhibitor) and are highly selective for FTase over GGTase I (geranylgeranyltransferase I). They are not substrates for farnesylation, do not have peptidic features, and have no hydrolyzable bonds. Structure- activity studies reveal the importance of the position of the carboxylic acid on the aryl ring as well as the reduction of the cysteine amide bond. Substitution at the 2-position of 4-amino-3'-carboxybiphenyl increases inhibitory potency, while the removal of the carboxylic acid results in a 10- fold loss of inhibitory activity.
- Qian, Yimin,Vogt, Andreas,Sebti, Sa?d M.,Hamilton, Andrew D.
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p. 217 - 223
(2007/10/03)
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- Pseudopeptide Inhibitors of Ras Farnesyl-Protein Transferase
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Inhibitors of Ras farnesyl-protein transferase are described.These are reduced pseudopeptides related to the C-terminal tetrapeptide of the Ras protein that signals farnesylation.Deletion of the carbonyl groups between the first two residues of the tetrap
- Graham, Samuel L.,deSolms, S. Jane,Giuliani, Elizabeth A.,Kohl, Nancy E.,Mosser, Scott D.,et al.
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p. 725 - 732
(2007/10/02)
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