7689-60-3Relevant articles and documents
Synthesis of non-natural cofactor analogs of S-adenosyl-L-methionine using methionine adenosyltransferase
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Page/Page column 37; 38, (2018/02/28)
The present disclosure relates to the synthesis of non-natural analogs of S-adenosyl-L-methionine (SAM) and/or of Se-adenosyl-L-methionine (SeAM) by reacting a methionine analog and adenosine triphosphate (ATP) in the presence of at least one methionine adenosyltransferase (MAT), and to use thereof with downstream SAM and/or SeAM utilizing enzymes. The non-natural analogs of SAM and/or SeAM have the general formula: where X is S or Se, and R1 is an alkyl group.
A sensitive mass spectrum assay to characterize engineered methionine adenosyltransferases with S-alkyl methionine analogues as substrates
Wang, Rui,Zheng, Weihong,Luo, Minkui
, p. 11 - 19 (2014/03/21)
Methionine adenosyltransferases (MATs) catalyze the formation of S-adenosyl-l-methionine (SAM) inside living cells. Recently, S-alkyl analogues of SAM have been documented as cofactor surrogates to label novel targets of methyltransferases. However, these chemically synthesized SAM analogues are not suitable for cell-based studies because of their poor membrane permeability. This issue was recently addressed under a cellular setting through a chemoenzymatic strategy to process membrane-permeable S-alkyl analogues of methionine (SAAMs) into the SAM analogues with engineered MATs. Here we describe a general sensitive activity assay for engineered MATs by converting the reaction products into S-alkylthioadenosines, followed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) quantification. With this assay, 40 human MAT mutants were evaluated against 7 SAAMs as potential substrates. The structure-activity relationship revealed that, besides better engaged SAAM binding by the MAT mutants (lower Km value in contrast to native MATs), the gained activity toward the bulky SAAMs stems from their ability to maintain the desired linear SN2 transition state (reflected by higher kcat value). Here the I117A mutant of human MATI was identified as the most active variant for biochemical production of SAM analogues from diverse SAAMs.
Ring size of somatostatin analogues (ODT-8) modulates receptor selectivity and binding affinity
Erchegyi, Judit,Grace, Christy Rani R.,Samant, Manoj,Cescato, Renzo,Piccand, Veronique,Riek, Roland,Reubi, Jean Claude,Rivier, Jean E.
, p. 2668 - 2675 (2008/12/22)
The synthesis, biological testing, and NMR studies of several analogues of H-c[Cys3-Phe6-Phe7-DTrp8-Lys 9-Thr10-Phe11-Cys14]-OH (ODT-8, a pan-somatostatin analogue, 1)
