- Late Stage Phosphotyrosine Mimetic Functionalization of Peptides Employing Metallaphotoredox Catalysis
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Access to phosphotyrosine (pTyr) mimetics requires multistep syntheses, and therefore late stage incorporation of these mimetics into peptides is not feasible. Here, we develop and employ metallaphotoredox catalysis using 4-halogenated phenylalanine to afford a variety of protected pTyr mimetics in one step. This methodology was shown to be tolerant of common protecting groups and applicable to the late stage pTyr mimetic modification of protected and unprotected peptides, and peptides of biological relevance.
- Brzozowski, Martin,Chen, Hao,Mao, Runyu,Nguyen, Nghi H.,Sleebs, Brad E.
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supporting information
p. 4244 - 4249
(2021/06/28)
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- PENTAFLUOROPHOSPHATE DERIVATIVE, ITS USES AND AN APPROPRIATE MANUFACTURING METHOD
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The invention relates to a pentafluorophosphate derivative according to general formula (I): or a pharmaceutically acceptable salt or solvate thereof. Thereby, R1 and R2 denote independently from each other H or F; R3 denotes H, an optionally substituted C1-C10 alkyl, an optionally substituted C3-C10 cycloalkyl, or an optionally substituted C6-C20 aryl, wherein a hydrocarbon chain of the alkyl, the cycloalkyl or the aryl can be interrupted by one or more oxygen, sulfur and/or nitrogen atoms; and M denotes any cation; with the proviso that at least one of R1 and R2 denotes F, if R3 denotes H. The invention further relates to uses of such a pentafluorophosphate derivative and to an appropriate manufacturing method.
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- An Intrinsic Hydrophobicity Scale for Amino Acids and Its Application to Fluorinated Compounds
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More than 100 hydrophobicity scales have been introduced, with each being based on a distinct condensed-phase approach. However, a comparison of the hydrophobicity values gained from different techniques, and their relative ranking, is not straightforward
- Hoffmann, Waldemar,Langenhan, Jennifer,Huhmann, Susanne,Moschner, Johann,Chang, Rayoon,Accorsi, Matteo,Seo, Jongcheol,Rademann, J?rg,Meijer, Gerard,Koksch, Beate,Bowers, Michael T.,von Helden, Gert,Pagel, Kevin
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supporting information
p. 8216 - 8220
(2019/05/21)
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- C-Glycosyl amino acids through hydroboration-cross-coupling of exo-glycals and their application in automated solid-phase synthesis
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O-Glycosylation is one of the most important post-translational modifications of proteins. The attachment of carbohydrates to the peptide backbone influences the conformation as well as the solubility of the conjugates and can even be essential for binding to specific ligands in cell-cell interactions or for active transport over membranes. This makes glycopeptides an interesting class of compounds for medical applications. To enhance the long-term availability of these molecules in vivo, the stabilization of the glycosidic bond between the amino acid residue and the carbohydrate is of interest. The described modular approach affords β-linked C-glycosyl amino acids by a sequence of Petasis olefination of glyconolactones, stereoselective hydroboration and a mild B-alkyl-Suzuki coupling reaction. The coupling products were transformed to C-glycosyl amino acid building-blocks suitable for solid-phase synthesis and successfully incorporated into a partial sequence of the tumor-associated MUC1-glycopeptide. The resulting C-glycopeptides are candidates for the development of long-term stable mimics of O-glycopeptide vaccines. Copyright
- Koch, Stefan,Schollmeyer, Dieter,L?we, Holger,Kunz, Horst
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p. 7020 - 7041
(2013/07/05)
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- An unnatural amino acid that mimics phosphotyrosine
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By replacing the phosphate group in pTyr with an isoxazole carboxylic acid, a novel unnatural amino acid has been successfully synthesized. Subsequently, its incorporation into a known PPI (protein-protein interaction) inhibitor of STAT3 protein (ISS 610)
- Ge, Jingyan,Wu, Hao,Yao, Shao Q.
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supporting information; experimental part
p. 2980 - 2982
(2010/08/04)
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- Synthesis and binding studies of two new macrocyclic receptors for the stereoselective recognition of dipeptides
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We present here the design, synthesis, and analysis of a series of receptors for peptide ligands inspired by the hydrogen-bonding pattern of protein β-sheets. The receptors themselves can be regarded as strands 1 and 3 of a three-stranded β-sheet, with crosslinking between the chains through the 4-position of adjacent phenylalanine residues. We also report on the conformational equilibria of these receptors in solution as well as on their tendency to dimerize. 1H NMR titration experiments are used to quantify the dimerization constants, as well as the association constant values of the 1:1 complexes formed between the receptors and a series of diamides and dipeptides. The receptors show moderate levels of selectivity in the molecular recognition of the hydrogen-bonding pattern present in the diamide series, selecting the α-amino acid-related hydrogen-bonding functionality. Only one of the two cyclic receptors shows modest signs of enantioselectivity and moderate diastereoselectivity in the recognition of the enantiomers and diastereoisomers of the Ala-Ala dipeptide (DDG0 1 (DD-DL) = -1.08 kcal/mol and DDG0 1(DD-LD) = -0.89 kcal/mol). Surprisingly, the linear synthetic precursors show higher levels of stereoselectivity than their cyclic counterparts.
- Castilla, Ana Maria,Ballester, Pablo,Conn, M. Morgan
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supporting information; experimental part
(2010/07/18)
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- Expanding the scope of PNA-encoded libraries: divergent synthesis of libraries targeting cysteine, serine and metallo-proteases as well as tyrosine phosphatases
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Seven PNA-encoded combinatorial libraries targeting proteases and phosphatases with covalent reversible and irreversible mechanism-based inhibitors were prepared. The libraries were synthesized using modified PNA monomers, which dramatically increase the water solubility of the libraries in biologically relevant buffers. The libraries were shown to selectively inhibit targeted enzymes.
- Debaene, Fran?ois,Da Silva, Julien A.,Pianowski, Zbigniew,Duran, Fernando J.,Winssinger, Nicolas
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p. 6577 - 6586
(2008/02/05)
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- Synthesis and cell-based activity of a potent and selective protein tyrosine phosphatase 1B inhibitor prodrug
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Our laboratory recently reported the development of novel prodrug chemistry for the intracellular delivery of phosphotyrosine mimetics. This chemistry has now been adapted for the synthesis of a prodrug that delivers the nonhydrolyzable difluoromethylphos
- Boutselis, Irene G.,Yu, Xiao,Zhang, Zhong-Yin,Borch, Richard F.
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p. 856 - 864
(2007/10/03)
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- PRODRUGS OF DRUG-PHOSPHATE CONJUGATES AND ANALOGS THEREOF
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Phosphate-substituted therapeutic compounds and analogs thereof that may serve as prodrugs are described. The prodrugs may include phosphorus-containing compounds, drug-phosphate conjugates, and analogs of drug-phosphate conjugates. Also described are ana
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Page/Page column 31
(2010/10/20)
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- A facile solution and solid phase synthesis of phosphotyrosine mimetic L-4-[diethylphosphono(difluoromethyl)]-phenylalanine (F2Pmp(EtO)2) derivatives
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The F2Pmp derivatives were prepared in 80-90% yield from commercially available protected L-4-iodophenylalanine by esterification with diazomethane followed by a CuCl-mediated coupling to (diethylphosphonyl) difluoromethylcadmium bromide. Moreover, treatment of L-4-iodoPhe-containing peptides under the same coupling conditions provided the F2Pmp-containing peptides in very good yields.
- Qabar, Maher N.,Urban, Jan,Kahn, Michael
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p. 11171 - 11178
(2007/10/03)
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