Our collaborative work with The Liu group has focused on elucidating molecular level details of natural product interactions with their putative cellular receptors. This has typically included initial SAR studies with natural products available through our total synthesis efforts or via methods developed for natural product derivatization. This information is then utilized to synthesize a suitable cellular probe for affinity chromatography experiments to identify putative cellular receptors. In one long-standing project, we determined that pateamine A and derivatives interact with elongation initiation factor 4A (eIF4A) essential for protein translation initiation.
Covalent Modification of a Cysteine in XPB Through Single Epoxide Cleavage of the Transcription Inhibitor Triptolide He, Q.-L.; Titov, D. V.; Li, J.; Tan, M.; Ye, Z.; Zhao, Y.; Romo, D.; Liu, J. O. Angew. Chem. Int. Ed. 2015, 54, 1859–1863.
Diazo Reagents with Small Steric Footprints for Simultaneous Arming/SAR Studies of Alcohol-Containing Natural Products via OH Insertion Chamni, S.; He, Q.L.; Dang, Y.; Bhat, S.; Liu, J.O.; Romo, D. ACS Chem. Biol., 2011, 6, 1175-1181. [Featured on Issue 11, 2011 Front Cover]
Inhibition of Nonsense-mediated mRNA Decay by the Natural Product Pateamine A Through Eukaryotic Initiation Factor 4AIII Dang, Y.; Low, W-K.; Xu, J.; Gehring, N. H.; Dietz, H.C.; Romo, D.; Liu, J.O. J. Biol. Chem., 2009, 35, 23613-23621.
Simultaneous Arming and Structure/Activity Studies of Natural Products Employing O-H Insertions: An Expedient and Versatile Strategy for Natural Products-Based Chemical Genetics Peddibhotla, S.; Dang, Y.; Liu, J. O.; Romo, D. J. Am. Chem. Soc., 2007, 129, 12222-12231. [Highlighted in C&EN, October 1, 2007]
Substrate-Dependent Targeting of Eukaryotic Translation Initiation Factor 4A by Pateamine A: Negation of Domain-Linker Regulation of Activity Low, W.-K.; Dang, Y.; Bhat, S.; Romo, D.; Liu, J. O. Chem. & Biol., 2007, 14, 1-13.
Isolation and Identification of Eukaryotic Initiation Factor 4A as a Molecular Target for the Marine Natural Product Pateamine A Low, W.-K.; Dang, Y.; Schneider-Poetsch, T.; Shi, Z.; Choi, N. S.; Rzasa, R. M.; Shea, H. A.; Li, S.; Park, K.; Ma, G.; Romo, D.; Liu, J. O. Methods in Enzymology 2007, 431, 303-324.
Daniel Romo, Jun O. Liu, N. S. Choi, Potent, Simplified Derivatives of Pateamine A U.S. Patent Issued June 12, 2007. Patent # US 7,230,021 B2.
Our collaborative work with The Molinski group includes de novo synthesis of natural products using cell-free enzyme preparations derived from the producing-marine sponges with synthetic, labeled biosynthetic precursors.
De Novo Synthesis of Benzosceptrin C and Nagelamide H from 7-15N-Oroidin: Implications for Pyrrole–Aminoimidazole Alkaloid Biosynthesis Stout E.P.; Morinaka, B.I.; Wang, Y.-G.; Romo, D.; Molinski, T.F. J. Nat. Prod., 2012, 75, 527-530.
Pyrrole-Aminoimidazole Alkaloid Metabiosynthesis with Marine Sponges Agelas Conifera and Stylissa Caribica Stout, E.P.; Wang, Y.-G.; Romo, D.; Molinski, T.F. Angew. Chem. Int. Ed., 2012, 51, 4877-4881.
Synthesis of 7-15N-Oroidin and Evaluation of Utility for Biosynthetic Studies of Pyrrole-Imidazole Alkaloids by Microsale 1H-15N HSQC and FTMS Wang, Y.; Morinaka, B.I.; Reyes, J.C.P.; Wolff, J. H.; Romo, D.; Molinski, T. F. J. Nat. Prod., 2010, 73, 428-434.
Our collaborative work with The Tantillo group involves quantum chemical computations that examine the mechanisms of laboratory experimentations in order to assess the nature of reactions.
Acylammonium Salts as Dienophiles in Diels-Alder/Lactonization Organocascades Abbasov, M. E.; Hudson, B. M.; Tantillo, D. J.; Romo D. J. Am. Chem. Soc. 2014, 136, 4492–4495. [Featured in JACS Spotlights, Synfacts, and Advances in Engineering]
Dyotropic Rearrangements of Fused Tricyclic β-Lactones: Application to the Synthesis of (−)-Curcumanolide A and (−)-Curcumalactone Leverett C.A.; Purohit V.C.; Johnson A.G.; Davis R.L.; Tantillo D.J.; Romo D. J. Am. Chem. Soc., 2012, 134, 13348-13356.
Switching Between Concerted and Stepwise Mechanisms for Dyotropic Rearrangements of β-Lactones Leading to Spirocyclic, Bridged γ-Butyrolactones Davis, R.; Leverett, C.; Romo, D.; Tantillo, D. J. Org. Chem., 2011, 76, 7167-7174.
Our 3-way collaborative efforts with The Cravatt and Rodríguez Groups involve simultaneous arming and SAR studies of bioactive natural products provided by the Rodríguez Group leading to bioactive cellular probes, which then enables proteome profiling with these natural product derivatives to identify cellular targets in the Cravatt Group. Recent work has focused on the anticancer, diterpenes eupalmerin acetate and eupalmerolide.
Simultaneous Structure–Activity Studies and Arming of Natural Products by C–H Amination Reveal Cellular Targets of Eupalmerin Acetate Li, J.; Cisar, J.S.; Zhou, C.-Y.; Vera, B.; Williams, H.; Rodrı´guez, A.B.; Cravatt, B.F.; Romo, D. Nature Chem., 2013, 5, 510-517.