135944-07-9Relevant articles and documents
The effects of conformational constraints and steric bulk in the amino acid moiety of philanthotoxins on AMPAR antagonism
J?rgensen, Malene R.,Olsen, Christian A.,Mellor, Ian R.,Usherwood, Peter N. R.,Witt, Matthias,Franzyk, Henrik,Jaroszewski, Jerzy W.
, p. 56 - 70 (2007/10/03)
Philanthotoxin-343 (PhTX-343), a synthetic analogue of wasp toxin PhTX-433, is a noncompetitive antagonist at ionotropic receptors (e.g., AChR or iGluR). To determine possible effects of variations of the amino acid side chain, a library consisting of seventeen PhTX-343 analogues was prepared. Thus, tyrosine was replaced by either apolar, conformationally constrained, or bulky amino acids, whereas the acyl unit and the polyamine moiety were kept unchanged. Analogues with tertiary amide groups were prepared for the first time. Pentafluorophenyl esters were employed for amide bond formation, establishing general protocols for philanthotoxin solution- and solid-phase synthesis (39-90% and 42-54% overall yields, respectively). The analogues were tested for their ability to antagonize kainate-induced currents of 2-amino-3-(3-hydroxy-5-methyl- 4-isoxazoyl)propanoic acid receptors (AMPAR) expressed in Xenopus oocytes from rat brain mRNA. This showed that steric bulk in the amino acid moiety is well tolerated and suggests that binding to AMPAR does not involve the α-NHCO group as a donor in hydrogen bonding.
Solid-phase synthesis and utilization of side-chain reactive unnatural amino acids
O'Donnell, Martin J.,Alsina, Jordi,Scott, William L.
, p. 8403 - 8406 (2007/10/03)
Alkylation of the benzophenone imine of glycine Wang resin with α,ω-dihaloalkanes yielded valuable reactive intermediates. These racemic ω-chloro or ω-bromo intermediates were converted to α-amino acids containing diverse side-chain functionalities (e.g.
Development of highly potent inhibitors of Ras farnesyltransferase possessing cellular and in vivo activity
Leftheris, Katerina,Kline, Toni,Vite, Gregory D.,Cho, Young H.,Bhide, Rajeev S.,Patel, Dinesh V.,Patel, Manorama M.,Schmidt, Robert J.,Weller, Harold N.,Andahazy, Mary L.,Carboni, Joan M.,Gullo-Brown, Johnni L.,Lee, Francis Y. F.,Ricca, Carol,Rose, William C.,Yan, Ning,Barbacid, Mariano,Hunt, John T.,Meyers, Chester A.,Seizinger, Bernd R.,Zahler, Robert,Manne, Veeraswamy
, p. 224 - 236 (2007/10/03)
Analogs of CVFM (a known nonsubstrate farnesyltransferase (FT) inhibitor derived from a CA2A2X sequence where C is cysteine, A is an aliphatic residue, and X is any residue) were prepared where phenylalanine was replaced by (Z)-dehyd
