- Engineered Substrate for Cyclooxygenase-2: A Pentapeptide Isoconformational to Arachidonic Acid for Managing Inflammation
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Beyond the conventional mode of working of anti-inflammatory agents through enzyme inhibition, herein, COX-2 was provided with an alternate substrate. A proline-centered pentapeptide isoconformational to arachidonic acid, which exhibited appreciable selectivity for COX-2, overcoming acetic acid- and formalin-induced pain in rats to almost 80%, was treated as a substrate by the enzyme. Remarkably, COX-2 metabolized the pentapeptide into small fragments consisting mainly of di- and tripeptides that ensured the safe breakdown of the peptide under in vivo conditions. The kinetic parameter Kcat/Km for COX-2-mediated metabolism of the peptide (6.3 × 105 M-1 s-1) was quite similar to 9.5 × 105 M-1 s-1 for arachidonic acid. Evidenced by the molecular dynamic studies and the use of Y385F COX-2, it was observed that the breakage of the pentapeptide has probably been taken place through H-bond activation of the peptide bond by the side chains of Y385 and S530.
- Kaur, Baljit,Kaur, Manpreet,Kaur, Navjot,Garg, Saweta,Bhatti, Rajbir,Singh, Palwinder
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p. 6363 - 6376
(2019/07/08)
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- Synthesis of selenoxo peptides and oligoselenoxo peptides employing LiAlHSeH
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Synthesis of selenoxo peptides by the treatment of Nα- protected peptide esters with a combination of PCl5 and LiAlHSeH is delineated. The method is simple, high-yielding, and free from racemization. Thus obtained selenoxo peptides are used as units for N-terminal chain extension through Nα-deprotection/coupling to yield peptide-selenoxo peptide hybrids. Multiple selenation is demonstrated by conversion of two peptide bonds of tripeptides into selenoxo peptide bonds. Amino acid derived arylamides are also converted into aryl selenoamides. C6H 5-CSeNH-Val-OMe 8f is obtained as single crystal, and its structure was determined through X-ray diffraction study.
- Vishwanatha,Narendra,Chattopadhyay, Basab,Mukherjee, Monika,Sureshbabu, Vommina V.
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experimental part
p. 2689 - 2702
(2012/06/01)
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- Chemical ligation of S-scylated cysteine peptides to form native peptides via 5-, 11-, and 14-membered cyclic transition states
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Cysteine-containing dipeptides 3a-l, (3b+3b′) (compound numbers in parentheses are used to indicate racemic mixtures; thus (3b+3b′) is the racemate of 3b and 3b′), and tripeptide 13 were synthesized in 68-96% yields by acylation of cysteine with N-(Pg-α-aminoacyl)- and N-(Pg-α-dipeptidoyl)benzotriazoles (where Pg stands for protecting group in the nomenclature for peptides throughout the paper) in the presence of Et3N. Cysteine-containing peptides 3a-l and 13 were S-acylated to give S-(Pg-α-aminoacyl)dipeptides 5a-l and S-(Pg-α-aminoacyl) tripeptide 14 without racemization in 47-90% yields using N-(Pg-α- aminoacyl)benzotriazoles 2 in CH3CN-H2O (7:3) in the presence of KHCO3. (In our peptide nomenclature, the prefixes di-, tri-, etc. refer to the number of amino acid residues in the main peptide chain; amino acid residues attached to sulfur are designated as S-acyl peptides. Thus we avoid use of the prefix "iso".) Selective S-acylations of serine peptide 3k and threonine peptide 3l containing free OH groups were thus achieved in 58% and 72% yield, respectively. S-(Pg-α-aminoacyl)cysteines 4a,b underwent native chemical ligations to form native dipeptides 3f,i via 5-membered cyclic transition states. Microwave irradiation of S-(Pg-α-aminoacyl)tripeptide 15 and S-(Pg-α-aminoacyl)tetrapeptide 17 in the presence of NaH2PO4/Na2HPO 4 buffer solution at pH 7.8 achieved chemical ligations, involving intramolecular migrations of acyl groups, via 11- and 14-membered cyclic transition states from the S-atom of a cysteine residue to a peptide terminal amino group to form native peptides 19 and 20 in isolated yields of 26% and 23%, respectively.
- Katritzky, Alan R.,Tala, Srinivasa R.,Abo-Dya, Nader E.,Ibrahim, Tarek S.,El-Feky, Said A.,Gyanda, Kapil,Pandya, Keyur M.
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scheme or table
p. 85 - 96
(2011/04/12)
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- Total Synthesis of Thymosin β4, 3. Conventional Synthesis of the Fragment of Thymosin β4
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As part of our total synthesis of thymosin β4, an optimized synthesis of the C-terminal part of thymosin β4 is described.Side chain functional residues of the tridecapeptide are masked by tert-butyl and the α-amino-acids residues are protected by the Z groups.The fully protected peptide derivative was obtained by WSCI/HOBt coupling of three fragments representing the segments , and . Key words: Thymosin β4; fragment ; peptide; solution synthesis; thymosins.
- Link, Peter,Voelter, Wolfgang
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p. 1000 - 1008
(2007/10/02)
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- DIASTEREOSELECTIVE HYDROGENATION OF MONODEHYDRO ENKEPHALINS CONTROLLED BY CHIRAL RHODIUM CATALYSTS
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Protected (Z)dehydrophenylalanyl-Leu-enkephalin, (Z)dehydrotyrosyl-Leu-enkephalin and (Z)dehydrotyrosyl-(R)Ala2-Leu-enkephalin, have been synthesized.These compounds have been hydrogenated to give protected Leu-enkephalins in the presence of various chiral rhodium complexes.Deprotection of the product gave Leu-enkephalins or epimers, ytterbium in liquid ammonia allows smooth deprotection of NHCBz or OTs groups on small amounts of peptides.Strong stereocontrol could be achieved by suitable choice of the chiral catalyst.This method has good potential for stereospecific labelling of enkephalins and other small peptides.
- Hammadi, A.,Nuzillard, J. M.,Poulin, J. C.,Kagan, H. B.
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p. 1247 - 1262
(2007/10/02)
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- Amino alcohols as C-Terminal Protecting Groups in Peptide Synthesis
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The synthesis of peptides using amino alcohols as C-terminal protecting groups is described.C-Terminal protection of amino acid could be accomplished by reduction of the terminal carboxyl group to a hydroxymethyl group, and regeneration of the carboxyl group could be achieved by Jones' oxidation.This method was applied to the formation of di- and tripeptides.
- Kashima, Choji,Harada, Kazuo,Fujioka, Yoko,Maruyama, Tatsuya,Omote, Yoshimori
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p. 535 - 540
(2007/10/02)
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- PREPARATION AND PROPERTIES OF A NEW DALARGINE ANALOGUE L-Tyr-D-Ala-Gly-L-Phe-L-Tle-L-Arg
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Stepwise synthesis in solution provided tert-butyloxycarbonyl-O-benzyl-L-tyrosyl-D-alanyl-glycyl-L-phenylalanyl-L-tert-leucyl-L-arginine which was then catalytically reduced and treated with trifluoroacetic acid.The product was purified by ion exchange ch
- Pospisek, Jan,Bespalova, Zhanna D.,Kovarikova, Eva,Titov, Michail I.,Barth, Tomislav,Medzihradszky, Kalman
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p. 1867 - 1871
(2007/10/02)
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- Peptide-bond Formation, Chemoselective Acylation of Amino Acids, and Crosslinking Reaction between Amino Acids Utilizing a Functional Five-membered Heterocycle, 1,3-Thiazolidine-2-thione
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The monitored aminolysis of 3-acyl-1,3-thiazolidine-2-thiones has been extended to the peptide-bond formation, the chemoselective acylation of amino acids having multifunctional groups, and the crosslinking reaction between amino acids.
- Nagao, Yoshimitsu,Miyasaka, Tadayo,Seno, Kaoru,Fujita, Eiichi,Shibata, Daisuke,Doi, Etsushiro
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p. 2439 - 2446
(2007/10/02)
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- OPIOID-LIKE PEPTIDES. PART I. HYDRAZIDE AND SOME AMIDES OF 2-Leu-ENKEPHALIN
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Synthesis and pharmacological properties of hydrazide, methylamide, 2-aminoethylamide, dimethylamide and butylamide of 2-Leu-enkephalin are described.
- Grzonka, Zbigniew,Palacz, Zbigniew,Baran, Leokadia,Przegalinski, Edmund,Kupryszewski, Gotfryd
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p. 1025 - 1035
(2007/10/02)
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- MONITORED AMINOLYSIS OF 3-ACYL-1,3-THIAZOLIDINE-2-THIONE WITH AMINO ACID AND ITS DERIVATIVE: PEPTIDE BOND FORMATION, CHEMOSELECTIVE ACYLATION, AND BRIDGING REACTION
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As a new extention of the monitored aminolysis of 3-acyl-1,3-thiazolidine-2-thione, its applications to peptide bond formation, chemoselective acylation of amino acid, and bridging reaction on the enzyme model are reported.
- Nagao, Yoshimitsu,Miyasaka, Tadayo,Seno, Kaoru,Yagi, Masahiro,Fujita, Eiichi
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p. 463 - 466
(2007/10/02)
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