37571-13-4Relevant articles and documents
Design and synthesis of Hsp90 inhibitors: Exploring the SAR of Sansalvamide A derivatives
Sellers, Robert P.,Alexander, Leslie D.,Johnson, Victoria A.,Lin, Chun-Chieh,Savage, Jeremiah,Corral, Ricardo,Moss, Jason,Slugocki, Tim S.,Singh, Erinprit K.,Davis, Melinda R.,Ravula, Suchitra,Spicer, Jamie E.,Oelrich, Jenna L.,Thornquist, Andrea,Pan, Chung-Mao,McAlpine, Shelli R.
experimental part, p. 6822 - 6856 (2010/10/18)
Utilizing the structure-activity relationship we have developed during the synthesis of the first two generations and mechanism of action studies that point to the interaction of these molecules with the key oncogenic protein Hsp90, we report here the design of 32 new Sansalvamide A derivatives and their synthesis. Our new structures, designed from previously reported potent compounds, were tested for cytotoxicity on the HCT116 colon cancer cell line, and their binding to the biological target was analyzed using computational studies involving blind docking of derivatives using Autodock. Further, we show new evidence that our molecules bind directly to Hsp90 and modulate Hsp90's binding with client proteins. Finally, we demonstrate that we have integrated good ADME properties into a new derivative.
Synthesis of second-generation Sansalvamide A derivatives: Novel templates as potential antitumor agents
Rodriguez, Rodrigo A.,Pan, Po-Shen,Pan, Chung-Mao,Ravula, Suchitra,Lapera, Stephanie,Singh, Erinprit K.,Styers, Thomas J.,Brown, Joseph D.,Cajica, Julia,Parry, Emily,Otrubova, Katerina,McAlpine, Shelli R.
, p. 1980 - 2002 (2007/10/03)
We report the synthesis of 34 second-generation Sansalvamide A derivatives. San A derivatives have unique anticancer properties and target multiple cancers, including colon, pancreatic, breast, prostate, and melanoma. As novel templates, the derivatives d
A single point chiral inversion that selforganizes a randomcoil peptide. Apolar solvent conformation of Boc-(L/D)-Glu-Ala-Leu-LysNHMe
Bobde,Beri,Rawale,Satyanarayana,Durani
, p. 3077 - 3086 (2007/10/02)
The tetrapeptide Boc-L-Glu-Ala-Leu-LysNHMe (1) reveals a random coil conformation, based on its Glu(γ) and Lys(ε) methylene proton aniosotropic shift, GluNH chemical shift, NOEs in the chloroform-DMSO (6:1), and its amide proton temperature coefficients in DMSO, while on similar considerations, the diastereomer Boc-D-Glu-Ala-Leu-LysNHMe (2) is characterized as a highly ordered 3/10 type distorted protohelix with a remarkably stable intramolecular salt bridge under these solvent conditions.
