4864-38-4Relevant academic research and scientific papers
Aza-peptidyl michael acceptor and epoxide inhibitors - Potent and selective inhibitors of Schistosoma mansoni and Ixodes ricinus legumains (asparaginyl endopeptidases)
Ovat, Asli,Muindi, Fanuel,Fagan, Crystal,Brouner, Michelle,Hansell, Elizabeth,Dvo?ák, Jan,Sojka, Daniel,Kopá?ek, Petr,McKerrow, James H.,Caffrey, Conor R.,Powers, James C.
experimental part, p. 7192 - 7210 (2010/07/05)
Aza-peptide Michael acceptors and epoxides with the general structure of YCO-Ala-Ala-AAsn-trans-CH=CHCOR and YCO-Ala-Ala-AAsn-EP-COR, respectively, are shown to be potent inhibitors of asparaginyl endopeptidases (legumains) from the bloodfluke, Schistosoma mansoni (SmAE), and the hard tick, Ixodes ricinus (IrAE). Structure-activity relationships (SARs) were determined for a set of 41 aza-peptide Michael acceptors and eight aza-peptide epoxides. Both enzymes prefer disubstituted amides to monosubstituted amides in the P10 position, and potency increased as we increased the hydrophobicity of the inhibitor in this position. Extending the inhibitor to P5 resulted in increased potency, especially against IrAE, and both enzymes prefer small over large hydrophobic residues at P2. Aza-peptide Michael acceptor inhibitors are more potent than aza-peptide epoxide inhibitors, and for some of these compounds, second-order inhibiton rate constants are the fastest yet discovered. Given the central functions of these enzymes in both parasites, the data presented here may facilitate the eventual design of selective antiparasitic drugs.
Supramolecular bidentate ligands by metal-directed in situ formation of antiparallel β-sheet structures and application in asymmetric catalysis
Laungani, Andy C.,Slattery, John M.,Krossing, Ingo,Breit, Bernhard
experimental part, p. 4488 - 4502 (2009/05/07)
The principles of protein structure design, molecular recognition, and supramolecular and combinatorial chemistry have been applied to develop a convergent metal-ion-assisted self-assembly approach that is a very simple and effective method for the de novo design and the construction of topologically predetermined antiparallel β-sheet structures and self-assembled catalysts. A new concept of in situ generation of bidentate P-ligands for transition-metal catalysis, in which two complementary, monodentate, peptide-based ligands are brought together by employing peptide secondary structure motif as constructing tool to direct the self-assembly process, is achieved through formation of stable β-sheet motifs and subsequent control of selectivity. The supramolecular structures were studied by 1H, 31P, and 13C NMR spectroscopy, ESI mass spectrometry, X-ray structure analysis, and theoretical calculations. Our initial catalysis results confirm the close relationship between the self-assembled sheet conformations and the catalytic activity of these metallopeptides in the asymmetric rhodium-catalyzed hydroformylation. Good catalyst activity and moderate enantioselectivity were observed for the selected combination of catalyst and substrate, but most importantly the concept of this new methodology was successfully proven. This work presents a perspective interface between protein design and supramolecular catalysis for the design of β-sheet mimetics and screening of libraries of self-organizing supramolecular catalysts.
The role of protecting groups in the formation of organogels through a nano-fibrillar network formed by self-assembling terminally protected tripeptides
Das, Apurba K.,Bose, Partha Pratim,Drew, Michael G.B.,Banerjee, Arindam
, p. 7432 - 7442 (2008/02/05)
A series of eight synthetic self-assembling terminally blocked tripeptides have been studied for gelation. Some of them form gels in various aromatic solvents including benzene, toluene, xylene, and chlorobenzene. It has been found that the protecting groups play an important role in the formation of organogels. It has been observed that, if the C-terminal has been changed from methyl ester to ethyl ester the gelation property does not change significantly (keeping the N-terminal protecting group same), while the change of the protecting group from ethyl ester to isopropyl ester completely abolishes the gelation property. Similarly, keeping the identical C-terminal protecting group (methyl ester) the results of the gelation study indicate that the substitution of N-terminal protection Boc- (tert-butyloxycarbonyl) to Cbz- (benzyloxycarbonyl) does change the gelation property insignificantly, while the change from Boc- to pivaloyl (Piv-) or acetyl (Ac-) group completely eliminates the gelation property. Morphological studies of the dried gels of two of the peptides indicate the presence of an entangled nano-fibrillar network that might be responsible for gelation. FTIR studies of the gels demonstrate that an intermolecular hydrogen bonding network is formed during gelation. Results of X-ray powder diffraction studies for these gelator peptides in different states (dried gels, gel, and bulk solids) reflected that the structure in the wet gel is distinctly different from the dried gel and solid state structures. Single crystal X-ray diffraction studies of a non-gelator peptide, which is structurally similar to the gelator molecules reveal that the peptide forms an antiparallel β-sheet structure in crystals.
Method for synthesis of C2-symmetric diamino diol mediated by titanium complexes
-
Page/Page column 2; 3, (2008/06/13)
A method for synthesis of C2-symmetric diamino diol mediated by titanium complexes is provided. A substituted-L-phenylalaninal undergoes pinacol coupling to yield the corresponding C2-symmetric (1S,2R,3R,4S)-1,4-diamino 2,3-diol in the presence of Cp2TiCl2/ZnCl2 and zinc metal, mediated in good yield and highly selective. This titanium-catalyzed reaction yields diaminodiol, offering a convenient alternative method to the synthesis of C2-symmetric peptidic protease inhibitors. Consequently, the method allows to synthesize TL-3 via titanium complex in moderate yield.
Structures, sensory activity, and dose/response functions of 2,5-diketopiperazines in roasted cocoa nibs (Theobroma cacao)
Stark, Timo,Hofmann, Thomas
, p. 7222 - 7231 (2007/10/03)
The taste compounds inducing the blood-like, metallic bitter taste sensation reported recently for a dichloromethane extract prepared from roasted cocoa nibs were identified as a series of 25 diketopiperazines by means of HPLC degustation, LC-MS/MS, and i
Scavenging of fluorinated N,N′-dialkylureas by hydrogen binding: A novel separation method for fluorous synthesis
Palomo, Claudio,Aizpurua, Jesus M.,Loinaz, Iraida,Fernandez-Berridi, Maria Jose,Irusta, Lourdes
, p. 2361 - 2364 (2007/10/03)
(matrix presented) A dramatic solubility increase in fluorous solvents is observed for N,N′-di(polyfluoroalkyl)ureas when hydrogen binding complexes are formed with commercially available perfluoroalkanoic acid scavengers. As a case example, analytically pure peptides and esters are obtained using this novel separation method.
A novel kinetically-controlled peptide synthesis - Dramatic increase of chemical yield with retention of chiral integrity
Shieh, Wen-Chung,Carlson, John A.,Shore, Michael E.
, p. 7167 - 7170 (2007/10/03)
Peptide synthesis employing the highly selective reaction of isobutyl chloroformate at the carboxyl group of the N-protected amino acid, almost to the exclusion of the amino group of the C-protected amino acid, is described. This one-stage, kinetically-controlled strategy remarkably affords peptides with excellent optical purity in high chemical yields.
Tandem deprotection-coupling of N(α)-Alloc-amino acids by use of ternary systems Pd cat./PhSiH3/carboxy-activated amino acid
Thieriet, Nathalie,Gomez-Martinez, Paloma,Guibe, Francois
, p. 2505 - 2508 (2007/10/03)
N(α)-allyloxycarbonyl derivatives of amino acids undergo smooth coupling with various carboxy-activated partners when treated with phenylsilane (PhSiH3) in the presence of catalytic amounts of tetrakis- (triphenylphosphine) palladium.
Carboxylic sulfonic mixed anhydrides: General utility and application to the synthesis of ceftazidime
Wirth
, p. 1535 - 1540 (2007/10/02)
A high-yielding acylation process which utilizes a mixed anhydride of the type RCO2SO2CH3 for the synthesis of the cephalosporin ceftazidime is detailed. The mixed anhydride is conveniently prepared by addition of methanesulfonyl chloride to the triethylammonium salt of the acid 2a. Although known for some time, these anhydrides have not been used often in acylations. This lack of general utility is explained by side reactions, especially formation of the carboxylic symmetric anhydride in sterically unhindered systems.
Comparative study of selected coupling reagents in dipeptide synthesis
Dudash Jr.,Jiang,Mayer,Joullie
, p. 349 - 356 (2007/10/02)
A comparative study of the effectiveness of selected coupling reagents in dipeptide synthesis was conducted. Included in the study were a new coupling agent, pentafluorophenyl diphenylphosphinate (FDPP, 1), benzotriazol-1-yl-oxytris(dimethylamino)phosphon
