Total Synthesis and Immunosuppressive Activity of (−)-Pateamine A and Related Compounds:  Implementation of a β-Lactam-Based Macrocyclization

Romo, Daniel; Rzasa, Robert M.; Shea, Hélène A.; Park, Kaapjoo; Langenhan, Joseph M.; Sun, Luo; Akhiezer, and Alexander; Liu, Jun O.

doi:10.1021/ja981846u

Cited by 157 publications

(114 citation statements)

References 54 publications

Supporting

Mentioning

110

Contrasting

Unclassified

Order By: Relevance

“…Reagents-PatA, DMDA-PatA, and biotinylated PatA were synthesized as previously reported (26,27,31). CHX and puromycin were purchased from Sigma-Aldrich.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Nonsense-mediated mRNA Decay by the Natural Product Pateamine A through Eukaryotic Initiation Factor 4AIII

Dang¹,

Low²,

Xu³

et al. 2009

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Nonsense-mediated mRNA decay (NMD) in mammalian cells is a key mechanism for the removal of mRNA containing premature stop codons and is mediated by the coordinated function of numerous proteins that dynamically associate with the exon junction complex. The information communicated by these interactions and the functional consequences from a mechanistic perspective, however, are not completely documented. Herein, we report that the natural product pateamine A (PatA) is capable of inhibiting NMD through direct interaction with eIF4AIII, which is independent of its inhibition of translation initiation. Furthermore, we have characterized the mechanisms by which PatA and cycloheximide modulate NMD. Unlike CHX, PatA was found to inhibit NMD by a novel mechanism that is independent of the phosphorylation of Up-frameshift protein 1.In mammalian cells, nonsense-mediated mRNA decay (NMD) 2 is one of the key RNA surveillance mechanisms to specifically degrade mRNA with premature stop codons (PTCs) located more than 50 -55 nucleotides upstream of the final exon-exon junction. PTCs can be formed in genes containing a nonsense mutation or frameshift mutation or as a result of errors that occur during transcription or RNA splicing (1-4). After splicing, the exon junction complex (EJC) imprints mature mRNAs 20 -24 nucleotides upstream of the exon-exon junction (5). The EJC is a dynamic multiprotein complex that plays an essential role in NMD. The core EJC proteins eIF4AIII, Y14, Magoh, and MLN51 form a platform to interact with several other proteins in a dynamic fashion to regulate NMD (6). The spatial-temporal regulation of NMD by the EJC and its partner proteins has been extensively investigated, leading to the proposition of the "linear interaction model" (4, 7). According to this model, deposition of the EJC onto mRNA causes the Y14-Magoh and eIF4AIII complex to effectively recruit Upf3 that interacts with Upf2. Although the mechanism of loading Upf1 onto EJC is poorly understood, it has been shown that phosphorylation and dephosphorylation of Upf1 by SMG-1, -5, -6, and -7 affect the interaction with the EJC complex through

show abstract

“…Reagents-PatA, DMDA-PatA, and biotinylated PatA were synthesized as previously reported (26,27,31). CHX and puromycin were purchased from Sigma-Aldrich.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Nonsense-mediated mRNA Decay by the Natural Product Pateamine A through Eukaryotic Initiation Factor 4AIII

Dang¹,

Low²,

Xu³

et al. 2009

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…One instance relates to stereoselective preparation of enyne 31 (Fig. 5c), a compound used to prepare immunosuppressant and anti-cancer 48 natural product pateamine A 49 . Conversion of E - 7 to homoallylic silyl ether 30 involved enantiomerically pure and commercially available S -propylene oxide, and was accomplished in two straightforward steps.…”

Section: Synthesis Of Biologically Active Compoundsmentioning

confidence: 99%

Synthesis of E- and Z-trisubstituted alkenes by catalytic cross-metathesis

Nguyen

Koh

Mann

et al. 2017

Nature

View full text Add to dashboard Cite

Catalytic cross-metathesis is a central transformation in chemistry, and yet, corresponding methods for stereoselectively generating acyclic trisubstituted alkenes in either isomeric form do not exist. The key problems are lack of chemoselectivity, namely, the preponderance of side reactions involving only the less hindered starting alkene, ensuing nonproductive processes of homo-metathesis byproducts, and formation of short-lived methylidene complexes. In contrast, in catalytic cross-coupling, another widely used process, substrates are more distinct and homocoupling is less of a problem. Here, we show that through cross-metathesis reactions involving E- or a Z-trisubstituted alkenes, easily prepared from commercially available starting materials by cross-coupling processes, many otherwise desirable and difficult-to-access linear E- or Z-trisubstituted alkenes can be synthesized efficiently and in exceptional stereoisomeric purity (up to >98% E or 95% Z). Utility is highlighted through concise stereoselective syntheses of biologically active compounds such as indiacen B (anti-fungal) and coibacin D (anti-inflammatory).

show abstract

“…All of these compounds are amenable to chemical synthesis. [232][233][234] Hippuristanol is an allosteric inhibitor of RNA binding to eIF4A. It shows a 10-fold increased specificity to eIF4A-I vs. eIF4A-III due to differences in the binding pockets, 158 demonstrating that selective pharmacological targeting of RNA helicases is possible.…”

mentioning

confidence: 99%