- 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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- 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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- 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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- 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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