- The Relation Between Position and Chemical Composition of Bis-Indole Substituents Determines Their Interactions with G-Quadruplex DNA
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G-quadruplex (G4) DNA structures are linked to fundamental biological processes and human diseases, which has triggered the development of compounds that affect these DNA structures. However, more knowledge is needed about how small molecules interact with G4 DNA structures. This study describes the development of a new class of bis-indoles (3,3-diindolyl-methyl derivatives) and detailed studies of how they interact with G4 DNA using orthogonal assays, biophysical techniques, and computational studies. This revealed compounds that strongly bind and stabilize G4 DNA structures, and detailed binding interactions which for example, show that charge variance can play a key role in G4 DNA binding. Furthermore, the structure–activity relationships generated opened the possibilities to replace or introduce new substituents on the core structure, which is of key importance to optimize compound properties or introduce probes to further expand the possibilities of these compounds as tailored research tools to study G4 biology.
- Prasad, Bagineni,Das, Rabindra Nath,Jamroskovic, Jan,Kumar, Rajendra,Hedenstr?m, Mattias,Sabouri, Nasim,Chorell, Erik
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supporting information
p. 9561 - 9572
(2020/07/09)
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- PHOTOREACTIVE COLLAGEN-LIKE PEPTIDES
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A novel 34 amino acid long collagen-like peptide rich in proline, hydroxyproline, and glycine, and with several photoreactive N-acyl-7-nitroindoline units incorporated into the peptide backbone was synthesized by on-resin fragment condensation. The circular dichroism measurement of this peptide supports a stable triple helix structure. This peptide has potential as a new biomimetic material with built-in latent photochemical functions that enable the decomposition into small peptide fragments by illumination with UV light of 350 nm. Using a photoreactive glycine derivative as a model compound for the collagen-like peptide, we demonstrate that its photolysis can also be triggered by a two-photon absorption process using a femtosecond laser at 710 nm. When a thin film of this compound is irradiated with femtosecond laser light at 710 nm the photochemistry occurs only at locations of irradiation. In addition, the collagen-like peptide is able to support mesenchymal stem cell growth, indicating its non-toxicity to these cells and its potential in tissue engineering applications.
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Paragraph 0092
(2019/04/30)
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- Synthesis and characterization of a photocleavable collagen-like peptide
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A 34-amino acid long collagen-like peptide rich in proline, hydroxyproline, and glycine, and with four photoreactive N-acyl-7-nitroindoline units incorporated into the peptide backbone was synthesized by on-resin fragment condensation. Its circular dichroism supports a stable triple helix structure. The built-in photochemical function enables the decomposition of the peptide into small peptide fragments by illumination with UV light of 350 nm in aqueous solution. Illumination of a thin film of the peptide, or a thin film of a photoreactive amino acid model compound containing a 5-bromo-7-nitroindoline moiety, with femtosecond laser light at 710 nm allows for the creation of well-resolved micropatterns. The cytocompatibility of the peptide was demonstrated using human mesenchymal stem cells and mouse embryonic fibroblasts. Our data show that the full-length peptide is cytocompatible as it can support cell growth and maintain cell viability. In contrast, the small peptide fragments created by photolysis are somewhat cytotoxic and therefore less cytocompatible. These data suggest that biomimetic collagen-like photoreactive peptides could potentially be used for growing cells in 2D micropatterns based on patterns generated by photolysis prior to cell growth.
- Li, Chunqiang,Ornelas, Alfredo,Williams, Kaitlyn N.,Hatch, Kevin A.,Paez, Aurelio,Aguilar, Angela C.,Ellis, Cameron C.,Tasnim, Nishat,Ray, Supriyo,Dirk, Carl W.,Boland, Thomas,Joddar, Binata,Michael, Katja
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p. 1000 - 1013
(2018/02/19)
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- A rapid and clean synthetic approach to cyclic peptides: Via micro-flow peptide chain elongation and photochemical cyclization: Synthesis of a cyclic RGD peptide
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A cyclic RGD peptide was efficiently synthesized based on micro-flow, triphosgene-mediated peptide chain elongation and micro-flow photochemical macrolactamization. Our approach enabled a rapid (amidation for peptide chain elongation 5 s, macrolactamization 5 min) and clean (only one column chromatographic separation) synthesis of a cyclic peptide.
- Mifune, Yuto,Nakamura, Hiroyuki,Fuse, Shinichiro
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p. 11244 - 11249
(2016/12/09)
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- Light-sensitive protecting groups for amines and alcohols: The photosolvolysis of n-substituted 7-nitroindolines
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Representative examples of primary and secondary amines were protected as urea derivatives 4 of 5-bromo-7-nitroindoline and even more efficiently as ureas 8 derived from 5,7-dinitroindoline, via high-yield reactions with carbamoyl chlorides 3 and 7, respectively. Deprotection of 4 or 8 was achieved in high yields by UV irradiation at room temperature in Pyrex vessels under neutral conditions and exclusion of air. In a similar manner the dinitroindolines serve as protecting groups for alcohols and phenols; the derived carbamates 5 and 9 can likewise be deprotected photochemically in high yields. Georg Thieme Verlag Stuttgart.
- Hassner, Alfred,Yagudayev, Diana,Pradhan, Tarun K.,Nudelman, Abraham,Amit, Boaz
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p. 2405 - 2409
(2008/03/27)
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- Bioavailable acyl-CoA : Cholesterol acyltransferase inhibitor with anti- peroxidative activity: Synthesis and biological activity of novel indolinyl amide and urea derivatives
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We synthesized a series of indoline derivatives with an amide or urea moiety and examined their inhibitory effects on acyl-CoA : cholesterol acyltransferase (ACAT) activity, lipid-peroxidation and serum cholesterol levels in experimental animals. Among the derivatives synthesized, a series of N-(1-alkyl-4,6- dimethylindolin-7-yl)-2,2-dimethylpropanamides potently inhibited rabbit intestinal ACAT activity and lipid-peroxidation of rat brain homogenate. The effect on ACAT activity was related to the length of the alkyl chain at the 1-position of indoline. N-(4,b-Dimethyl-1-octylindolin-7- yl)-2,2-dimethylpropanamide hydrochloride (55) showed inhibitory effects on intestinal and hepatic ACAT activity slightly weaker than those of YM-750, and an inhibitory effect on low density lipoprotein (LDL)-peroxidation similar to that of probucol. Compound 55 also reduced serum cholesterol at 10 mg/kg/d in hyperlipidemic rats and 20 mg/kg/d in normolipidemic hamsters. The plasma concentration of 55 reached 716 ng/ml in dogs (10 mg/kg, p.o.), which is an effective concentration against hepatic ACAT activity and LDL- peroxidation. In conclusion, compound 55 is a novel bioavailable ACAT inhibitor with anti-peroxidative activity and is thus a promising anti- atherosclerotic and anti-hyperlipidemic drug. Indoline proved to be a useful pharmacophore for molecular design of new anti-peroxidative drugs.
- Kamiya, Shoji,Shirahase, Hiroaki,Yoshimi, Akihisa,Nakamura, Shohei,Kanda, Mamoru,Matsui, Hiroshi,Kasai, Masayasu,Takahashi, Kenji,Kurahashi, Kazuyoshi
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p. 817 - 827
(2007/10/03)
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- Heterobicyclic sulfonamide and sulfonic ester derivatives
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Novel heterobicyclic sulfonamide and sulfonic ester derivatives represented by the following general formula(I), which exhibit an antitumor activity and are lowly toxic, and processes for the preparation thereof. A sulfonamide derivative and a sulfonic ester derivative represented by the general formula (I) or a pharmacologically acceptable salt thereof: STR1 wherein A represents a monocyclic or bicyclic aromatic ring which may be substituted; B represents a six-membered unsaturated hydrocarbon ring or a six-membered unsaturated heterocycle containing one nitrogen atom, each of which may be substituted; C represents a five-membered heterocycle containing one or two nitrogen atoms which may be substituted; W represents a single bond or a group represented by formula --CH=CH--; X represents a group represented by formula --N(R1)-- or oxygen; Y represents carbon or nitrogen; Z represents a group represented by formula --N(R2)-- or nitrogen; and R1 and R2 may be the same or different from each other and each represent hydrogen or lower alkyl.
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