Pateamine

Isolation and Identification of Eukaryotic Initiation Factor 4A as a Molecular Target for the Marine Natural Product Pateamine A 303... 

Synthesis of a Bioactive Biotin-Pateamine A (B-PatA) Conjugate 313... 

Figure 5.2 SG and PB formation in response to different stresses. U20S cells were subjected to some of the stresses described inTable 5.1, then stained as indicated. Untreated cells display few PBs and no SGs, whereas arsenite treatment (0.5 mM, 45 min, panels B and H) strongly induces assembly of both PBs and SGs. Clotrimazole (C, I), pateamine A (D, J), and heat shock (F, L) induce more SGs than PBs, whereas emitine treatment (E, K) abolishes PBs and does not induce SGs. Note that YB-1 is present in PBs in unstressed cells (A, red), but relocalizes to SGs upon most stress conditions (C, D, F, whereas p54/RCK (red, G, H, I, J, L) remains predominantly associated with PBs regardless of stress.

Dang, Y., Kedersha, N., Low, W. K., Romo, D., Gorospe, M., Kaufman, R., Anderson, P., and Liu, J. O. (2006). Eukaryotic initiation factor 2alpha-independent pathway of stress granule induction by the natural product pateamine A. J. Biol. Chem. 281, 32870-32878. 

Figure lZpl Total synthesis of (-)-Pateamine A.TBS, t-butyldimethylsilyl TIPS, triisopropyl silyl TCBoc, trichloro t-butoxycarbamate DIAD, diisopropyl azodicarboxylate. 

Synthesis of Derivatives of Pateamine A and Structure Activity Relationship Studies... 

Table 14.1 IL-2 reporter gene assay (transfected Jurkat T cells) activity of pateamine A and derivatives... 

Figure 14.3 Structures of Pateamine A (1), Boc-pateamine A (25), and DMDA-PatA (28). The putative binding (rigid regions, in red) and scaffolding (flexible and modifiable, in blue) domains are indicated and suggest possible sites for modification, namely, the C3- amino group.

Northcote, P. T., Blunt, J. W., andMunro, M. H. G. (1991). Pateamine A potent cytotoxin from the New Zealand marine sponge, Mycale sp. Tetrahedron Lett. 32, 6411—6414. 

Rzasa, R. M., Shea, H. A., and Romo, D. (1998). Total synthesis of the novel, immunosuppressive agent (-)-Pateamine A from Mycale sp. Employing a b-lactam-based macrocyclization. J. Am. Chem. Soc. 120, 591—592. 

The Zealandic marine area has been extensively explored, affording several unusual metabolites (Chart 7.10.A/PO). Alkaloids bearing a macrocarbocycle are produced by dinoflagellates. Red seaweeds give macrocyclic ethers. Demosponges are the source of both pateamine A, a strongly... 

Polyket mixed biogenesis macrolides (pateamine A from Mycale sp., Poecil., Porif from NZ Northcote 1991) macrocyclic ethers y-pyrones (Phaceiocarpus sp., Gigartinales, Rhodoph. from SE Australia and Tasmania Murray 1995). 

Pateamine (606), a potent cytotoxin containing a dilactone functionality, was isolated from a New Zealand species of Mycale and identified by analysis of spectral data [480]. Total synthesis of pateamine A (606) involved a (3-lactam based macrocyclisation [481,482], while another total synthesis of pateamine employed a concise and convergent route [483]. 

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