857026-04-1Relevant articles and documents
MODULATORS OF SESTRIN-GATOR2 INTERACTION AND USES THEREOF
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Paragraph 00347; 00348, (2018/11/22)
The present invention provides compounds, compositions thereof, and methods of using the same.
Remote C-H Hydroxylation by an α-Ketoglutarate-Dependent Dioxygenase Enables Efficient Chemoenzymatic Synthesis of Manzacidin C and Proline Analogs
Zwick, Christian R.,Renata, Hans
supporting information, p. 1165 - 1169 (2018/02/07)
Selective C-H functionalization at distal positions remains a highly challenging problem in organic synthesis. Though Nature has evolved a myriad of enzymes capable of such feat, their synthetic utility has largely been overlooked. Here, we functionally characterize an α-ketoglutarate-dependent dioxygenase (Fe/αKG) that selectively hydroxylates the ? position of various aliphatic amino acids. Kinetic analysis and substrate profiling of the enzyme show superior catalytic efficiency and substrate promiscuity relative to other Fe/αKGs that catalyze similar reactions. We demonstrate the practical utility of this transformation in the concise syntheses of a rare alkaloid, manzacidin C, and densely substituted amino acid derivatives with remarkable step efficiency. This work provides a blueprint for future applications of Fe/αKG hydroxylation in complex molecule synthesis and the development of powerful synthetic paradigms centered on enzymatic C-H functionalization logic.
MODULATORS OF SESTRIN-GATOR2 INTERACTION AND USES THEREOF
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Paragraph 0465, (2017/05/15)
The present invention provides compounds, compositions thereof, and methods of using the same.
HETEROCYCLIC KINASE INHIBITORS
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Page/Page column 149, (2016/05/19)
The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.
In situ deprotection and incorporation of unnatural amino acids during cell-free protein synthesis
Arthur, Isaac N.,Hennessy, James E.,Padmakshan, Dharshana,Stigers, Dannon J.,Lesturgez, Stéphanie,Fraser, Samuel A.,Liutkus, Mantas,Otting, Gottfried,Oakeshott, John G.,Easton, Christopher J.
, p. 6824 - 6830 (2013/06/26)
The S30 extract from E. coli BL21 Star (DE3) used for cell-free protein synthesis removes a wide range of α-amino acid protecting groups by cleaving α-carboxyl hydrazides; methyl, benzyl, tert-butyl, and adamantyl esters; tert-butyl and adamantyl carboxamides; α-amino form-, acet-, trifluoroacet-, and benzamides and sidechain hydrazides and esters. The free amino acids are produced and incorporated into a protein under standard conditions. This approach allows the deprotection of amino acids to be carried out in situ to avoid separate processing steps. The advantages of this approach are demonstrated by the efficient incorporation of the chemically intractable (S)-4-fluoroleucine, (S)-4,5- dehydroleucine, and (2S,3R)-4-chlorovaline into a protein through the direct use of their respective precursors, namely, (S)-4-fluoroleucine hydrazide, (S)-4,5-dehydroleucine hydrazide, and (2S,3R)-4-chlorovaline methyl ester. These results also show that the fluoroand dehydroleucine and the chlorovaline are incorporated into a protein by the normal biosynthetic machinery as substitutes for leucine and isoleucine, respectively. Copyright
Stereocontrolled synthesis of (S)-γ-fluoroleucine
Padmakshan, Dharshana,Bennett, Simon A.,Otting, Gottfried,Easton, Christopher J.
, p. 1083 - 1084 (2008/03/11)
Starting with (S)-leucine, the corresponding γ-fluoride 8 has been prepared in a stereocontrolled fashion, by exploiting methods for the direct side-chain bromination of amino acid derivatives and silven(I) fluoride as the fluorinating reagent. Georg Thieme Verlag Stuttgart.
