- Interaction of anti-thyroid drugs with iodine: The isolation of two unusual ionic compounds derived from Se-methimazole
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The inhibition of lactoperoxidase (LPO)-catalyzed iodination of l-tyrosine by the anti-thyroid drug methimazole (MMI) and its selenium analogue (MSeI) is described. MSeI inhibits LPO with an IC50 value of 12.4 M, and this inhibition could be completely reversed by increasing the peroxide concentration. In addition to the inhibition, MSeI reacts with molecular iodine to produce novel ionic diselenides, and the nature of the species formed in this reaction appear to be solvent-dependent. The formation of ionic species in the reaction is confirmed by single-crystal X-ray studies, FT-IR and FT-Raman spectroscopic investigations. This study provides the first experimental evidence that MSeI not only effectively inhibits the LPO-catalyzed iodination of tyrosine, but also reacts with I2 to produce novel ionic diselenides. These results also suggest that MSeI reacts with iodine, even in its oxidized form, to form ionic diselenides containing iodide or polyiodide anions, which might be effective intermediates in the inhibition of thyroid hormones. The Royal Society of Chemistry 2006.
- Roy, Gouriprasanna,Nethaji, Munirathinam,Mugesh
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- A novel class of tyrosine derivatives as dual 5-LOX and COX-2/mPGES1 inhibitors with PGE2 mediated anticancer properties
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Leukotriene and prostaglandin pathways are controlled by the enzymes, LOX and COX/mPGES1 respectively and are responsible for inflammatory responses. PGE2, produced by mPGES1, leads to the progression of inflammation as well as cancer. A series of 19 novel tyrosine derivatives are synthesized, characterized and tested against 5-LOX, in vitro, and production of PGE2, in HeLa cells. 6b-v and 6c-i, are found to possess maximum inhibitory action against 5-LOX and PGE2 production. The compound 6b-v is found to act by disrupting the redox cycle of the 5-LOX enzyme, and its activity is comparable to that of the commercial drug, Zileuton. The activity of the other compound 6c-i is comparable to a drug in clinical trials, Licofelone, and it has been found to inhibit the mRNA expression of mPGES1 predominantly. It also arrests the HeLa cells in the S and G2/M phases of the cell cycle indicating anticancer activity. Also, compounds, 6b-iv and 6b-viii inhibit both the LT & PG pathways in the inflammation cascade. Presence of iodine in the phenyl ring appears to favour the inhibition of 5-LOX whereas chlorine favours the inhibition of PGE2 production. These leads could be further optimized and developed as drugs against inflammation and cancer.
- Puratchikody, Ayarivan,Umamaheswari, Appavoo,Irfan, Navabshan,Sinha, Shweta,Manju,Ramanan, Meera,Ramamoorthy, Gayathri,Doble, Mukesh
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supporting information
p. 834 - 846
(2019/01/09)
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- An efficient synthesis of l-3,4,5-trioxygenated phenylalanine compounds from l-tyrosine
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A new strategy for the synthesis of l-3,4,5-trioxygenated phenylalanine derivatives from l-tyrosine is developed for the first time. The approach, featuring the transformation of aryl diiodide to bis-phenol via a one-pot procedure including lithiation, boronation, and oxidation, is highly practical. By this robust protocol, N-protected l-3,5-bis(tert-butyldimethylsilyloxy)-4- methoxy-phenylalanine and l-3,4,5-trimethoxy-phenylalanine derivatives were obtained from l-tyrosine in 9 steps with 36-40% overall yields.
- Chen, Ruijiao,Liu, Hao,Liu, Xiubing,Chen, Xiaochuan
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p. 3565 - 3570
(2013/04/24)
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- Solid phase synthesis of I25 labeled insulin fragments. Part III. Synthesis of 125-I-insulin fragment B15-18 Leu-Tyr(I2)-Leu-Val
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NOWA DAYS, synthesis of biological active peptides has been in an impressive success. This has been achieved by development of new techniques, using new reagents and easy reach. A new approach to radio-peptides synthesis has been investigated in an effort to overcome the technical difficulties of separation, purification and identification of the prepared peptide fragments. In a series of solid-phase peptide synthesis of labeled insulin fragments, we have prepared 125-I-Insulin fragment Bl 5-18. In this research work we discussed the synthesis of Insulin fragment B15-18 Labeled with Leu-Tyr(I 2)-Leu-Val.
- Zewail,Shalaby,Megahed
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p. 639 - 647
(2014/04/03)
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- First aromatic electrophilic iodination reaction on the solid-phase: Iodination of bioactive peptides
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Direct iodination of Tyr residues of peptides anchored on solid supports was accomplished, for the first time, by aromatic electrophilic attack of iodonium ions provided by the IPy2BF4 reagent. Compatibility studies of the iodination with routine solid-phase synthesis protocols are reported.
- Arsequell, Gemma,Espuna, Gemma,Valencia, Gregorio,Barluenga, Jose,Carlon, Raquel Perez,Gonzalez, Jose M.
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p. 7393 - 7396
(2007/10/03)
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- Prevention of Tryptophan Oxidation During Iodination of Tyrosyl Residues in Peptides
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Studies on model systems clearly revealed oxidative degradation of tryptophan under the usual conditions of iodination of tyrosine residues in peptides, whereby the rate of former reaction was found to be faster than the iodination itself.Nin-formylation of tryptophan brings about an efficient indole protection against this oxidative degradation. - Keywords: Iodination of Tyrosyl Residues, Oxidative Degradation of Tryptophan, Nin-Formyl Tryptophan
- Mourier, G.,Moroder, L.,Previero, A.
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p. 101 - 104
(2007/10/02)
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- The Tritium Kinetic Isotope Effect for the Iodination of L-(5-3H)-3-Iodotyrosine
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The kinetic tritium isotope effect (kH/kT) for the iodination of L-(5-3H)-3-iodotyrosine at pH 7.5 was found to be 4.29 +/- 0.25 with molecular iodine and 4.50 +/- 0.26 with chloramine-T/potassium iodide.This effect establishes that the rate-limiting step is proton removal by the general base.A novel method for measuring the fraction of tritiated water by high performance liquid chromatography is described.
- Baldas, John,Colmanet, Silvano,Porter, Quentin N.
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p. 1147 - 1151
(2007/10/02)
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