1160-54-9Relevant articles and documents
Collision-induced dissociative chemical cross-linking reagent for protein structure characterization: Applied Edman chemistry in the gas phase
Dreiocker, Frank,Mueller, Mathias Q.,Sinz, Andrea,Schaefer, Mathias
, p. 178 - 189 (2010)
Chemical cross-linking combined with a subsequent enzymatic digestion andmass spectrometric analysis of the created crosslinked products presents an alternative approach to assess low-resolution protein structures and to gain insight into protein interfaces. In this contribution, we report the design of an innovative cross-linker based on Edman degradation chemistry, which leads to the formation of indicative mass shifted fragment ions and constant neutral losses (CNLs) in electrospray ionization (ESI)-tandem-mass spectrometry (MS/MS) product ion mass spectra, allowing an unambiguous identification of cross-linked peptides. Moreover, the characteristic neutral loss reactions facilitate automated analysis by multiple reaction monitoring suited for high throughput studies with good sensitivity and selectivity. The functioning of the novel cross-linker relies on the presence of a highly nucleophilic sulfur in a thiourea moiety, safeguarding for effective intramolecular attack leading to predictive and preferred cleavage of a glycyl-prolyl amide bond. Our innovative analytical concept and the versatile applicability of the collision-induced dissociative chemical cross-linking reagent are exemplified for substance P, luteinizing hormone releasing hormone LHRH and lysozyme. The novel cross-linker is expected to have a broad range of applications for probing protein tertiary structures and for investigating protein-protein interactions. Copyright
A Chemical Model for the Activation of Pyruvate-Formate-Lyase
Baldwin, Jack E.,Brown, David,Scudder, Paul H.,Wood, Mark E.
, p. 2105 - 2108 (1995)
A chemical model is described for the activation of the carbon-centred radical-based enzyme, pyruvate-formate-lyase.The feasibility of a 5'-deoxyadensyl radical abstracting a hydrigen atom from C-2 of a peptideglycine residue has been demonstrated in an intramolecular process.
A new benzotriazole-mediated stereoflexible gateway to hetero-2,5- diketopiperazines
Monbaliu, Jean-Christophe M.,Hansen, Finn K.,Beagle, Lucas K.,Panzner, Matthew J.,Steel, Peter J.,Todadze, Ekaterina,Stevens, Christian V.,Katritzky, Alan R.
, p. 2632 - 2638 (2012/04/17)
Open chain Cbz-L-aa1-L-Pro-Bt (Bt=benzotriazole) sequences were converted into either the corresponding trans- or cis-fused 2,5- diketopiperazines (DKPs) depending on the reaction conditions. Thermodynamic tandem cyclization/epimerization afforded selectively the corresponding trans-DKPs (69-75%). Complementarily, tandem deprotection/cyclization led to the cis-DKPs (65-72%). A representative set of proline-containing cis- and trans-DKPs has been prepared. A mechanistic investigation, based on chiral HPLC, kinetics, and computational studies enabled a rationalization of the results. Stereoflexible route to DKPs: A convenient, versatile, and flexible benzotriazole-mediated methodology for the synthesis of proline-containing hetero-2,5-diketopiperazines (DKPs) is reported. Depending on the reaction conditions, either cis- or trans-configured DKPs were obtained starting from the same inexpensive l,l-dipeptidoyl benzotriazole key intermediate (see scheme). Kinetics, chiral HPLC, and computational studies forged a background for mechanistic rationalization. Copyright
Inhibition of prolyl oligopeptidase with a synthetic unnatural dipeptide
Racys, Daugirdas Tomas,Rea, Dean,Fueloep, Vilmos,Wills, Martin
supporting information; experimental part, p. 4775 - 4782 (2010/08/22)
A new inhibitor, containing a linked proline-piperidine structure, for the enzyme prolyl oligopeptidase (POP) has been synthesised and demonstrated to bind covalently with the enzyme at the active site. This provides evidence that covalent inhibitors of P
Use of 'click chemistry' for the synthesis of tetrazole-containing analogues of the neuroprotective agent glycyl-L-prolyl-L-glutamic acid
Hung, Kuo-Yuan,Harris, Paul W. R.,Brimble, Margaret A.
scheme or table, p. 1233 - 1236 (2009/09/06)
Tetrazole-containing analogues of glycyl-L-prolyl-L-glutamic acid (GPE) were prepared by coupling of Cbz-glycyl-L-proline with tetrazole-containing glutamic acids followed by hydrogenation of the resultant tripeptide. Synthesis of the tetrazole-containing glutamic acids involved 1,3-dipolar cycloaddition of sodium azide to nitrile derivatives of the corresponding glutamic acids. Georg Thieme Verlag Stuttgart.
Efficient peptide coupling involving sterically hindered amino acids
Katritzky, Alan R.,Todadze, Ekaterina,Angrish, Parul,Draghici, Bogdan
, p. 5794 - 5801 (2008/02/09)
(Chemical Equation Presented) Hindered amino acids have been introduced into peptide chains by coupling N-(Cbz- and Fmoc-α-aminoacyl) benzotriazoles with amino acids, wherein at least one of the components was sterically hindered, to provide compounds 3a-e, (3c +3 c′), 5a-d, (5a + 5a′), 6a-c, (6b + 6b′), 8a-c, 9a-e, 10a-d, and (10a + 10a′) in isolated yields of 41-95% with complete retention of chirality as evidenced by NMR and HPLC analysis. The benzotriazole activation methodology is a new route for the synthesis of sterically hindered peptides. (Note: compound numbers written within brackets represent diastereomeric mixtures or racemates; compound numbers without brackets represent enantiomers.)
Synthesis and neuroprotective activity of analogues of glycyl-L-prolyl-L- glutamic acid (GPE) modified at the α-carboxylic acid
Trotter, Nicholas S.,Brimble, Margaret A.,Harris, Paul W.R.,Callis, David J.,Sieg, Frank
, p. 501 - 517 (2007/10/03)
The synthesis of nine GPE* analogues, wherein the α-carboxylic acid group of glutamic acid has been modified, is described by coupling readily accessible N-benzyloxycarbonyl-glycyl-l-proline 2 with various analogues of glutamic acid. Pharmacological evaluation of the novel compounds was undertaken to further understand the role of the glutamate residue on the observed neuroprotective properties of the endogenous tripeptide GPE.
Conformational analysis of β-turn structure in tetrapeptides containing proline or proline analogs
Hayashi, Takashi,Asai, Tomohito,Ogoshi, Hisanobu
, p. 3039 - 3042 (2007/10/03)
In order to evaluate the influence of cyclic secondary amino acids on the stability of β-turn structure, we have prepared Ac-Gly-L-Xxx-L-Leu-Gly-N(CH3)2 (Xxx = Aze, 4-membered ring: 1, Xxx = Pro, 5-membered ring: 2, Xxx = Pip, 6-membered ring: 3). The NOE cross peaks that support β-turn structure were observed in 1-3. The NOE cross peak between both terminals of the synthetic peptides, however, was observed only in the NOESY spectra of 2. This result indicates that 5-membered ring side chain in proline plays a very important role in the formation of β-hairpin structure.
Amino acids and peptides. XVI. Synthesis of N-terminal tetrapeptide analogs of fibrin α-chain and their inhibitory effects on fibrinogen/thrombin clotting
Kawasaki,Hirase,Miyano,Tsuji,Iwamoto
, p. 3253 - 3260 (2007/10/02)
N-Terminal tetrapeptide analogs of fibrin α-chain were synthesized by the solution method using a new active ester, the ester of the oxime of p-nitroacetophenone, and by the solid-phase method. Their inhibitory effects on fibrinogen/thrombin clotting were examined. Of the synthetic peptides, amide analogs of Gly-Pro-Arg-Pro exhibited a more potent inhibitory effect.
