185063-17-6Relevant articles and documents
Synthesis and biological evaluation of analogs of AAL(S) for use as ceramide synthase 1 inhibitors
Toop, Hamish D.,Don, Anthony S.,Morris, Jonathan C.
, p. 11593 - 11596 (2015/12/08)
A convergent synthesis to access hydrophobic tail analogs and head group modifications of AAL(S) is described. The analogs synthesised were evaluated for their ability to inhibit ceramide synthase 1 and for their cytotoxicity in K562 cells. Our results ha
TX-2152: A conformationally rigid and electron-rich diyne analogue of FTY720 with in vivo antiangiogenic activity
Nakayama, Shinichi,Uto, Yoshihiro,Tanimoto, Kanako,Okuno, Yasuhiro,Sasaki, Yuki,Nagasawa, Hideko,Nakata, Eiji,Arai, Ken,Momose, Kaori,Fujita, Tetsuro,Hashimoto, Toshihiro,Okamoto, Yasuko,Asakawa, Yoshinori,Goto, Satoru,Hori, Hitoshi
experimental part, p. 7705 - 7714 (2009/04/06)
We designed FTY720 analogues with conformationally rigid and electron-rich acetylenic chains as antiangiogenic agents (the monoyne 1: TX-2148, the diyne 2: TX-2152, the triyne 3: TX-2256). Molecular orbital (MO) calculations of our designed acetylenic ana
Dose-response relations for unnatural amino acids at the agonist binding site of the nicotinic acetylcholine receptor: Tests with novel side chains and with several agonists
Kearney, Patrick C.,Nowak, Mark W.,Zhong, Wenge,Silverman, Scott K.,Lester, Henry A.,Dougherty, Dennis A.
, p. 1401 - 1412 (2007/10/03)
Structure-function relations in the nicotinic acetylcholine receptor are probed using a recently developed method based on chemical synthesis of nonsense suppressor tRNAs with unnatural amino acid residues, site-directed incorporation at nonsense codons in Xenopus laevis oocytes, and electrophysiological measurements. A broad range of unnatural amino acids, as many as 14 at a given site, are incorporated at three sites, α93, α190, and α198, all of which are tyrosine in the wild-type receptor and are thought to contribute to the agonist binding site. Confirming and expanding upon earlier studies using conventional mutagenesis, the three tyrosines are shown to be in substantially different structural microenvironments. In particular, a crucial role is established for the hydroxyl group of α-Tyr93, whereas a variety of substituents are functional at the analogous position of αTyr198. Interestingly, consideration of three different agonists (acetylcholine, nicotine, and tetramethylammonium) does not discriminate between these two best-characterized binding site residues. In addition, double-mutation studies establish the independent effects of mutations at the pore region (second transmembrane region) and at the agonist binding site, and this observation leads to a novel strategy for adjusting EC50 values. These results establish the broad generality and great potential of the unnatural amino acid methodology for illuminating subtle structural distinctions in neuroreceptors and related integral membrane proteins.