- Coupling-Reagent-Free Synthesis of Dipeptides and Tripeptides Using Amino Acid Ionic Liquids
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A general method for the synthesis of dipeptides has been developed, which does not require any coupling reagents. This method is based on the reaction of readily available HCl salts of amino acid methyl esters with tetrabutylphosphonium amino acid ionic liquids. The isolation procedure of stepwise treatment with AcOH is easy to carry out. The method was extended to the synthesis of tripeptide, tyrosyl-glycyl-glycine, present in IMREG-1, also.
- Furukawa, Shinya,Fukuyama, Takahide,Matsui, Akihiro,Kuratsu, Mai,Nakaya, Ryotaro,Ineyama, Takashi,Ueda, Hiroshi,Ryu, Ilhyong
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supporting information
p. 11980 - 11983
(2015/08/18)
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- Identification and characterization of prokaryotic dipeptidyl-peptidase 5 from porphyromonas gingivalis
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Porphyromonas gingivalis, a Gram-negative asaccharolytic anaerobe, is a major causative organism of chronic periodontitis. Because the bacterium utilizes amino acids as energy and carbon sources and incorporates them mainly as dipeptides, a wide variety of dipeptide production processes mediated by dipeptidyl-peptidases (DPPs) should be beneficial for the organism. In the present study, we identified the fourth P. gingivalis enzyme, DPP5. In a dpp4-7-11-disrupted P. gingivalis ATCC 33277, a DPP7-like activity still remained. PGN-0756 possessed an activity indistinguishable from that of the mutant, and was identified as a bacterial orthologue of fungal DPP5, because of its substrate specificity and 28.5% amino acid sequence identity with an Aspergillus fumigatus entity. P. gingivalis DPP5 was composed of 684 amino acids with a molecular mass of 77,453, and existed as a dimer while migrating at 66 kDa on SDS-PAGE. It preferred Ala and hydrophobic residues, had no activity toward Pro at the P1 position, and no preference for hydrophobic P2 residues, showed an optimal pH of 6.7 in the presence of NaCl, demonstrated Km and kcat/Km values for Lys-Ala-MCA of 688 μM and 11.02 μM-1 s-1, respectively, and was localized in the periplasm. DPP5 elaborately complemented DPP7 in liberation of dipeptides with hydrophobic P1 residues. Examinations of DPP- and gingipain gene-disrupted mutants indicated that DPP4, DPP5, DPP7, and DPP11 together with Arg- and Lys-gingipains cooperatively liberate most dipeptides from nutrient oligopeptides. This is the first study to report that DPP5 is expressed not only in eukaryotes, but also widely distributed in bacteria and archaea.
- Ohara-Nemoto, Yuko,Rouf, Shakh M. A.,Naito, Mariko,Yanase, Amie,Tetsuo, Fumi,Ono, Toshio,Kobayakawa, Takeshi,Shimoyama, Yu,Kimura, Shigenobu,Nakayama, Koji,Saiki, Keitarou,Konishi, Kiyoshi,Nemoto, Takayuki K.
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p. 5436 - 5448
(2014/03/21)
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- Synthetic peptide analogs of Arg-Pro-Pro-Gly-Phe as selective inhibitors of thrombin and thrombin activation of protease activated receptors 1 and 4
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The invention relates to compounds and methods for inhibiting human platelet aggregation, thrombosis and cell activation mediated by PAR1 and PAR4 using peptide analogs of Arg-Pro-Pro-Gly-Phe that contain one or more amino acid substitutions. The invention also includes screening methods for identifying compounds that inhibit thrombin mediated activities.
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Page/Page column 8-9
(2010/02/09)
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- Inhibitors of tripeptidyl peptidase II. 2. Generation of the first novel lead inhibitor of cholecystokinin-8-inactivating peptidase: A strategy for the design of peptidase inhibitors
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The cholecystokinin-8 (CCK-8)-inactivating peptidase is a serine peptidase which has been shown to be a membrane-bound isoform of tripeptidyl peptidase II (EC 3.4.14.10). It cleaves the neurotransmitter CCK-8 sulfate at the Met-Gly bond to give Asp-Tyr(SO3H)-Met-OH + Gly-Trp-Met-Asp-Phe-NH2. In seeking a reversible inhibitor of this peptidase, the enzymatic binding subsites were characterized using a fluorimetric assay based on the hydrolysis of the artificial substrate Ala-Ala-Phe-amidomethylcoumarin. A series of di- and tripeptides having various alkyl or aryl side chains was studied to determine the accessible volume for binding and to probe the potential for hydrophobic interactions. From this initial study the tripeptides Ile-Pro-Ile-OH (K(i) = 1 μM) and Ala-Pro-Ala-OH (K(i) = 3 μM) and dipeptide amide Val-Nvl-NHBu (K(i) = 3 μM) emerged as leads. Comparison of these structures led to the synthesis of Val-Pro-NHBu (K(i) = 0.57 μM) which served for later optimization in the design of butabindide, a potent reversible competitive and selective inhibitor of the CCK-8-inactivating peptidase. The strategy for this work is explicitly described since it illustrates a possible general approach for peptidase inhibitor design.
- Ganellin, C. Robin,Bishop, Paul B.,Bambal, Ramesh B.,Chan, Suzanne M. T.,Law, James K.,Marabout, Benoit,Luthra, Pratibha Mehta,Moore, Andrew N. J.,Peschard, Olivier,Bourgeat, Pierre,Rose, Christiane,Vargas, Froylan,Schwartz, Jean-Charles
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p. 664 - 674
(2007/10/03)
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- SYNTHESIS OF DIPEPTIDE ESTERS OF METRONIDAZOLE AND EVALUATION OF THEIR HYDROLYTIC STABILITY
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Amino acid and dipeptide esters of metronidazole were synthesized and evaluated on their hydrolytic stability in various buffers and culture media.The hydrolytic susceptibility of the different esters was minimal in the pH range 3-5.In the alkaline region, pH 6.5-8, the half-lifes were of the order of 1-6.6 hrs.At alkaline pH the dipeptide esters were more susceptible towards hydrolysis.At pH 8.8 the observed half-life for the gly-gly and the gly-phe esters was 0.2 h, whereas for the gly and the phe ester it was 1.1 h, respectively 2.7 h.It was demonstrated that the increased rate of hydrolysis for the dipeptide esters was due to an intramolecular aminolysis with the formation of a diketopiperazine accompanied by the release of free metronidazole.
- Permentier, Dirk,Vansteenkiste, Stefan,Schacht, Etienne,Vermeersch, Hans,Remon, Jean Paul
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p. 701 - 708
(2007/10/02)
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- NOUVELLE METHODE DE PROTECTION DU CARBOXYLE DES ACIDES a-AMINES: ESTERS 9-FLUORENYLIQUES
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The novel 9-fluorenyl esters of various L-a-aminoacids (N-protected or N-free) are easily obtained by the action of 9-diazofluorene on the aminoacid in the appropriate organic solvent.Such esters are cleanly cleaved by mild acidolysis or hydrogenolysis and can serve as amino-components in peptide synthesis.
- Proussios, Cleanthis,Kolovos, Miltiadis
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p. 3413 - 3414
(2007/10/02)
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- Pharmaceutical preparations having diuretic activity
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Pharmaceutical preparations having diuretic activity and comprising a peptide of the formula STR1 wherein (a) R1 and R2 are hydrogen and R3 is --OH, or STR2 or Y, or wherein (b) R1 is hydrogen, R2 is CH2 OH or STR3 and R3 is --OH or Y, or wherein (c) R1 is --CH2 OH and R2 is hydrogen or STR4 and R3 is --OH or Y, or wherein (d) R1 is STR5 R2 is hydrogen or --CH2 OH and R3 is --OH, --NHCH2 COOH, or Y, and wherein X is hydrogen, methyl, prolyl, or an N-protective group, and Y is --NH2, --OR4, wherein R4 is linear or branched alkyl or cyclolalkyl having from 1 to 8 carbon atoms, benzyl, phenyl, or STR6
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