103321-59-1Relevant articles and documents
N-(Benzoyloxy)amines: An investigation of their thermal stability, synthesis, and incorporation into novel peptide constructs
Nemchik, Anne,Badescu, Valentina,Phanstiel IV, Otto
, p. 4315 - 4325 (2003)
A series of N-benzoyloxyamines were pyrolyzed and their decomposition temperatures correlated well with the amine architecture's ability to stabilize a N-centered radical. A variety of amine substrates were treated with a biphasic mixture of benzoyl peroxide (BPO), CH2Cl2 and an aqueous carbonate buffer (at pH 10.5). Primary and secondary amines were successfully N-benzoyloxylated in good yield. Tertiary amines and BPO gave low yields of the corresponding N-oxide and complex product mixtures, presumably via radical decomposition. Electron deficient amines (such as fluorinated aliphatic amines, α-aminoacids, α-aminoesters, and α-aminoamides) were not N-benzoyloxylated under these conditions. Instead, N-benzoylation was observed with the fluorinated amines and the reaction was sensitive to temperature and the pH of the aqueous medium. A one-pot-two-step synthesis of Nα-FMOC-L-Leu-Nβ-(benzoyloxy)-β-alanine ethyl ester, a peptide containing both an α- and a novel β-amino acid framework, was also developed.
Simultaneous fluorescent monitoring of proteasomal subunit catalysis
Wakata, Aya,Lee, Hsien-Ming,Rommel, Philipp,Toutchkine, Alexei,Schmidt, Marion,Lawrence, David S.
, p. 1578 - 1582 (2010)
The proteasome, a multicatalytic protease, displays distinct chymotrypsin-like, caspase-like, and trypsin-like activities at three different subunits of the multimeric complex. Fluorescent substrates for each of these active sites have been described. However, since the fluorescent properties of these substrates are very similar, it is not possible to simultaneously monitor catalysis of two or more activities. We have developed a long wavelength ( λex = 600 nm, λem = 700 nm) fluorescent substrate for the chymotrypsinlike active site via a combinatorial library strategy. This peptide-based substrate is a highly selective proteasomal chymotrypsin-like sensor, as assessed by a series of proteasomal active site mutants in yeast cell lysates. A corresponding caged analog of the sensor has been prepared, which is resistant to proteolysis until activated by 349 nm light. The latter affords the opportunity to assess proteasomal activity with a high degree of temporal control. The distinct photophysical properties of the sensor allow the chymotrypsin-like activity to be simultaneously monitored during caspase-like or trypsin-like catalysis. We have found that chymotrypsin-like activity is enhanced in the presence of the trypsin-like substrate but reduced in the presence of caspase-like substrate. Furthermore, the chymotrypsin-like sensor hinders the activity of both the caspase- and trypsin-like active sites. Coincident monitoring of two catalytic active sites furnishes twothirds coverage of total proteasomal activity, which should provide the means to address if and how the distinct active sites of the proteasome influence one another during catalysis.
A New Route for the Total Synthesis of 6,7-Dihydroeponemycin
Bennacer, Bibia,Rivalle, Christian,Grierson, David S.
, p. 4569 - 4574 (2003)
A new synthesis of dihydroeponemycin (2), a peptide epoxide with potent cytotoxic and antiangiogenesis activity, has been developed. In the initial steps, Fmoc-Leu-Cl was converted into the key amino ketone intermediate 9 by Stille coupling with tributylvinyltin, conjugate addition of PhSA1Me 2 to the derived enone, S-oxidation, and heat-induced syn elimination. Subsequent reaction of 9 with H2O2 and catalytic Triton B produced the corresponding epoxides as a 1:1 diastereomeric mixture in 89 % yield. These epoxides were separated and individually converted into 2 and(2S)-epi-dihydroeponemycin (24) in a four-step "one-pot" protocol (77 % overall yield in both cases). Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
Orthogonal 19F-Labeling for Solid-State NMR Spectroscopy Reveals the Conformation and Orientation of Short Peptaibols in Membranes
Grage, Stephan L.,Kara, Sezgin,Bordessa, Andrea,Doan, Véronique,Rizzolo, Fabio,Putzu, Marina,Kuba?, Tomá?,Papini, Anna Maria,Chaume, Grégory,Brigaud, Thierry,Afonin, Sergii,Ulrich, Anne S.
supporting information, p. 4328 - 4335 (2018/02/26)
Peptaibols are promising drug candidates in view of their interference with cellular membranes. Knowledge of their lipid interactions and membrane-bound structure is needed to understand their activity and should be, in principle, accessible by solid-state NMR spectroscopy. However, their unusual amino acid composition and noncanonical conformations make it very challenging to find suitable labels for NMR spectroscopy. Particularly in the case of short sequences, new strategies are required to maximize the structural information that can be obtained from each label. Herein, l-3-(trifluoromethyl)bicyclopent[1.1.1]-1-ylglycine, (R)- and (S)-trifluoromethylalanine, and 15N-backbone labels, each probing a different direction in the molecule, have been combined to elucidate the conformation and membrane alignment of harzianin HK-VI. For the short sequence of 11 amino acids, 12 orientational constraints have been obtained by using 19F and 15N NMR spectroscopy. This strategy revealed a β-bend ribbon structure, which becomes realigned in the membrane from a surface-parallel state towards a membrane-spanning state, with increasing positive spontaneous curvature of the lipids.
Synthesis and in vitro stability of amino acid prodrugs of 6-β-naltrexol for microneedle-enhanced transdermal delivery
Eldridge, Joshua A.,Milewski, Mikolaj,Stinchcomb, Audra L.,Crooks, Peter A.
, p. 5212 - 5215 (2014/12/11)
A small library of amino acid ester prodrugs of 6-β-naltrexol (NTXOL, 1) was prepared in order to investigate the candidacy of these prodrugs for microneedle-enhanced transdermal delivery. Six amino acid ester prodrugs were synthesized (6a-f). 6b, 6d, and 6e were stable enough at skin pH (pH 5.0) to move forward to studies in 50% human plasma. The lead compound (6e) exhibited the most rapid bioconversion to NTXOL in human plasma (t1/2 = 2.2 ± 0.1 h).
