- Preparation method of non-natural amino acid N-fluorenylmethoxycarbonyl-beta-(2-thienyl)-D-alanine
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The invention discloses a preparation method of non-natural amino acid N-fluorenylmethoxycarbonyl-beta-(2-thienyl)-D-alanine, and mainly solves the technical problems that an original technology is complex in use, low in yield, high in cost, and the like. The preparation method comprises the steps of step I, carrying out chlorine acylation on 2-thiophene methanol through a chlorine acylating agent, so as to prepare 2-chloromethyl thiophene; step II, enabling 2-chloromethyl thiophene and diethyl acetamidomalonate to react through sodium ethoxide, so as to prepare 2-thienyl diethyl malonate; and step III, enabling 2-thienyl diethyl malonate subjected to alkaline saponification and L-acetyl transferase resolution to react with fmoc-groups, filtering an obtained L amino protection product, collecting a mother liquid, adding hydrochloric acid and a methyl alcohol solution for reflux reaction, monitoring the reaction process through NMR, adding fmoc-osu for reaction, tracking and monitoring the reaction process through TLC, and carrying out impurity extraction, acidification, and the like, to obtain the N-fluorenylmethoxycarbonyl-beta-(2-thienyl)-D-alanine.
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Paragraph 0016-0018; 0021-0023; 0026-0027; 0030-0031; 0038
(2017/05/13)
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- Novel selective inhibitors of the interaction of individual nuclear hormone receptors with a mutually shared steroid receptor coactivator 2
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Nuclear hormone receptor (NR) signaling, currently a therapeutic target in multiple diseases, involves an ordered series of protein interactions to regulate transcription in response to changing hormone levels. Later steps in the process of ligand-dependent signaling are driven by a highly conserved interaction between the NRs and the steroid receptor coactivators (SRCs) that is effected by a conserved interaction motif (L1XXL2L3), known as an NR box. Using computational design and combinatorial chemistry, we have produced novel ∞-helical proteomimetics of the second NR box of SRC2 that exploit structural differences between human estrogen receptor ∞ (hER∞), human estrogen receptor β (hERβ), and human thyroid hormone receptor β (hTRβ). The resulting library sequentially replaced each leucine with non-natural side chains. Screening this library using a quantitative competition assay revealed compounds that selectively inhibit the interaction of SRC2-2 with each individual NR in preference to its interaction with the other NR. This approach generated highly selective compounds from one that had no specificity for a particular family member. These compounds represent the first family-member-selective competitive inhibitors of the protein interactions of transcription factors. Copyright
- Geistlinger, Timothy R.,Guy, R. Kiplin
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p. 6852 - 6853
(2007/10/03)
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