- Photochemical formation of quinone methides from peptides containing modified tyrosine
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We have demonstrated that quinone methide (QM) precursors can be introduced in the peptide structure and used as photoswitchable units for peptide modifications. QM precursor 1 was prepared from protected tyrosine in the Mannich reaction, and further used as a building block in peptide synthesis. Moreover, peptides containing tyrosine can be transformed into a photoactivable QM precursor by the Mannich reaction which can afford monosubstituted derivatives 2 or bis-substituted derivatives 3. Photochemical reactivity of modified tyrosine 1 and dipeptides 2 and 3 was studied by preparative irradiation in CH3OH where photodeamination and photomethanolysis occur. QM precursors incorporated in peptides undergo photomethanolysis with quantum efficiency ΦR = 0.1-0.2, wherein the peptide backbone does not affect their photochemical reactivity. QMs formed from dipeptides were detected by laser flash photolysis (λmax ≈ 400 nm, τ = 100 μs-20 ms) and their reactivity with nucleophiles was studied. Consequently, QM precursors derived from tyrosine can be a part of the peptide backbone which can be transformed into QMs upon electronic excitation, leading to the reactions of peptides with different reagents. This proof of principle showing the ability to photochemically trigger peptide modifications and interactions with other molecules can have numerous applications in organic synthesis, materials science, biology and medicine.
- Husak, Antonija,Noichl, Benjamin P.,?umanovac Ramljak, Tatjana,Sohora, Margareta,?kalamera,Budi?a, Nediljko,Basari?, Nikola
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- COMPOUNDS, COMPOSITIONS AND METHODS FOR STABILIZING TRANSTHYRETIN AND INHIBITING TRANSTHYRETIN MISFOLDING
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Provided herein are compounds having activity against TTR related conditions, and pharmaceutically accepted salts and solvates thereof. Also provided are methods of using the compounds for inhibiting and preventing TTR aggregation and/or amyloid formation in the peripheral nerves, kidney, cardiac tissue, eye and CNS, and of treating a subject with peripheral TTR amyloidosis.
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Paragraph 0387-0389; 0639-0642
(2021/08/06)
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- Quantitative insight into the design of compounds recognized by the L-type amino acid transporter 1 (LAT1)
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L-Type amino acid transporter 1 (LAT1) is a transmembrane protein expressed abundantly at the blood-brain barrier (BBB), where it ensures the transport of hydrophobic acids from the blood to the brain. Due to its unique substrate specificity and high expression at the BBB, LAT1 is an intriguing target for carrier- mediated transport of drugs into the brain. In this study, a comparative molecular field analysis (CoMFA) model with considerable statistical quality (Q2=0.53, R2=0.75, Q2 SE=0.77, R2 SE=0.57) and good external predictivity (CCC=0.91) was generated. The model was used to guide the synthesis of eight new prodrugs whose affinity for LAT1 was tested by using an in situ rat brain perfusion technique. This resulted in the creation of a novel LAT1 prodrug with l-tryptophan as the promoiety; it also provided a better understanding of the molecular features of LAT1-targeted high-affinity prodrugs, as well as their promoiety and parent drug. The results obtained will be beneficial in the rational design of novel LAT1-binding prodrugs and other compounds that bind to LAT1.
- Ylikangas, Henna,Malmioja, Kalle,Peura, Lauri,Gynther, Mikko,Nwachukwu, Emmanuel O.,Lepp?nen, Jukka,Laine, Krista,Rautio, Jarkko,Lahtela-Kakkonen, Maija,Huttunen, Kristiina M.,Poso, Antti
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p. 2699 - 2707
(2015/02/02)
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- Design, synthesis and inhibition activity of novel cyclic peptides against protein tyrosine phosphatase A from Mycobacterium tuberculosis
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Mycobacterium tuberculosis, the causative agent for tuberculosis has employed several signalling molecules to sense the host cellular environment and act accordingly. For example, protein tyrosine phosphatase A (MPtpA) of M. tuberculosis, a signalling pro
- Chandra, Koushik,Dutta, Debajyoti,Das, Amit K.,Basak, Amit
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supporting information; scheme or table
p. 8365 - 8373
(2011/02/25)
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- tert-buyldiphenylsilylethyl ("TBDPSE"): A practical protecting group for phenols
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(Chemical Equation Presented) A new protection group for phenols, the 2-(tert-butyldiphenylsilyl)ethyl (TBDPSE) group, has been prepared and investigated. Protection of a variety of substituted phenols proceeds in good to excellent yield. The group is stable to mild acid, base, hydrogenolysis conditions, and lithium/ halogen exchange on the protected phenol. Removal is achieved with strong acid or standard fluoride treatment.
- Gerstenberger, Brian S.,Konopelski, Joseph P.
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p. 1467 - 1470
(2007/10/03)
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- Discovery and SAR of novel, potent and selective protein tyrosine phosphatase 1B inhibitors
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A salicylate second site binder was linked to three classes of phosphotyrosine mimetics to produce potent protein tyrosine phosphatase 1B (PTP1B) inhibitors which exhibit significant selectivity against other phosphatases including the most homologous mem
- Pei, Zhonghua,Li, Xiaofeng,Liu, Gang,Abad-Zapatero, Cele,Lubben, Tom,Zhang, Tianyuan,Ballaron, Stephen J.,Hutchins, Charles W.,Trevillyan, James M.,Jirousek, Michael R.
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p. 3129 - 3132
(2007/10/03)
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- Soluble alpha-amino acid salts in acetonitrile: practical technology for the production of some dipeptides.
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Alpha-amino acids are soluble in acetonitrile when treated with phosphazene bases. As a result, the protection/deprotection events that are usually required for peptide coupling reactions can be minimized. This is illustrated in the synthesis of the important angiotensin-converting enzyme (ACE) inhibitor enalapril. [reaction: see text]
- Palomo, Claudio,Palomo, Antonio L,Palomo, Francisco,Mielgo, Antonia
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p. 4005 - 4008
(2007/10/03)
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- The 2,4-dimethylpent-3-yloxycarbonyl (Doc) group as a new, nucleophile-resistant protecting group for tyrosine in solid phase peptide synthesis
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The 2,4-dimethylpent-3-yloxycarbonyl (Doc) group is presented as a new protecting group for tyrosine. The Doc group is 1000-fold more stable towards the nucleophile piperidine than the commonly used 2-bromobenzyloxycarbonyl (2-BrZ) group is, and it is completely cleaved by hydrogen fluoride.
- Rosenthal, Katri,Karlstroem, Amelie,Unden, Anders
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p. 1075 - 1078
(2007/10/03)
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- Peptide Synthesis in Aqueous Solution. V. Properties and Reactivities of (p-Hydroxyphenyl)benzylmethylsulfonium Salts for Direct Benzyl Esterification of N-Acylpeptides
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Some (p-hydroxyphenyl)benzylmethylsulfonium salts were prepared. These compounds generated a benzyl cation and converted not only N-acylamino acids but also N-acylpeptides into their corresponding benzyl esters without causing the racemization.
- Nakata, Takashi,Nakatani, Masaru,Takahashi, Masatoshi,Okai, Jiro,Kawaoka, Yoshiaki,Kouge, Katsushige,Okai, Hideo
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p. 1099 - 1106
(2007/10/03)
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- A TOTAL SYNTHESIS OF (+)-GEODIAMOLIDES A AND B, THE NOVEL CYCLODEPSIPEPTIDES
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Diastereo-controlled total synthesis of (+)-geodiamolides A (1) and B (2) has been accomplished via a prior synthesis of the tetrapropionate-derived fragment 7 and of the halogenated N-methyltyrosyltripeptide 6, the latter involving direct halogenation of the tripeptide 5, and subsequent coupling of both fragments followed by the trichlorobenzoyl chloride-mediated macrolactonization, respectively.
- Hirai, Yoshiro,Yakota, Katsuyuki,Yamazaki, Takao,Momose, Takefumi
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p. 1101 - 1119
(2007/10/02)
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