- Synthesis of the thyrotropin releasing hormone enantiomer and some diastereoisomers and in vitro studies of their biological activity
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The isomers of TRH with DDD, DLL, LDL, and LLD configurations were prepared unequivocally by coupling pentachlorophenyl pyroglutamate of the required configuration with the appropriate histidylprolinamide diastereoisomer. The dipeptide amide was made by c
- Flouret,Morgan,Gendrich,Wilber,Seibel
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- Mechanically Strong Heterogeneous Catalysts via Immobilization of Powderous Catalysts to Porous Plastic Tablets
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Main observation and conclusion: We describe a practical and general protocol for immobilization of heterogeneous catalysts to mechanically robust porous ultra-high molecular weight polyethylene tablets using inter-facial Lifshitz-van der Waals Interactions. Diverse types of powderous catalysts, including Cu, Pd/C, Pd/Al2O3, Pt/C, and Rh/C have been immobilized successfully. The immobilized catalysts are mechanistically robust towards stirring in solutions, and they worked well in diverse synthetic reactions. The immobilized catalyst tablets are easy to handle and reused. Moreover, the metal leaching of immobilized catalysts was reduced significantly.
- Li, Tingting,Xu, Bo
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supporting information
p. 2673 - 2678
(2021/08/03)
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- The microenvironment and pKaperturbation of aminoacyl-tRNA guided the selection of cationic amino acids
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The proteinogenic lysine (Lys) and arginine (Arg) have multiple methylene groups between α-carbon and the terminal charged centre. Why nature did not select ornithine (Orn), 2,4-diamino butyric acid (Dab) and 2,3-diamino propionic acid (Dpr) with fewer methylene groups in the side chain remains an important question! The propensity of aminoacyl-tRNA (aa-tRNA) model substrates towards self-degradationviaintramolecular lactamization was studied using UV spectroscopy and1H-NMR titration, which showed that Lys and Arg remain stable, and Orn and Dab cyclize to lactam. Hydrophobicity-assisted surface mediated model peptide formation highlighted that the microenvironment and pKaperturbation led to poor regioselectivity (α-aminevs.terminal amine) in Dpr and other non-proteinogenic analogues. The α-selectivity became even poorer in the presence of phosphate, making them ill-suited for peptide synthesis. Superior regioselectivity of the Lys aa-tRNA model substrate suggests that the extra methylene bridge helped nature to separate the microenvironments of the α-amine and ε-amine to synthesize the peptide backbone.
- Hazra, Bibhas,Prasad, Mahesh,Roy, Rajat,Tarafdar, Pradip K.
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supporting information
p. 8049 - 8056
(2021/10/04)
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- Synthesis method of N alpha-tert-butyloxycarbonyl-L-histidine
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The invention relates to a synthesis method of N alpha-tert-butyloxycarbonyl-L-histidine, which comprises the following steps of: dissolving solid L-histidine in a sodium carbonate water solution, dropwisely adding liquid di-tert-butyl dicarbonate, reacting, filtering, and washing the filtrate with an organic solvent to remove unreacted di-tert-butyl dicarbonate; after the reaction solution is subjected to aqueous phase acidification, adding an extracting agent ethyl acetate for extraction, conducting standing and layering, and washing, drying and filtering an oil phase to obtain an ethyl acetate solution containing an intermediate N alpha-tert-butyloxycarbonyl-Nim-tert-butyloxycarbonyl-L-histidine; stirring the ethyl acetate solution containing the intermediate N alpha-tert-butyloxycarbonyl-Nim-tert-butyloxycarbonyl-L-histidine at 50-100 DEG C for reaction, and after the reaction is finished, carrying out after-treatment to obtain the product N alpha-tert-butyloxycarbonyl-L-histidine.The synthesis method of N alpha-tert-butyloxycarbonyl-L-histidine provided by the invention is simple in process and convenient to operate, the product purity and yield are higher than those in the prior art, the technical problem that purification and desalination are not thorough by using ion exchange resin is solved, and the synthesis method is suitable for industrial production.
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Paragraph 0030; 0032-0033; 0035-0036; 0038-0039; 0041
(2020/09/09)
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- Easy-handling and low-leaching heterogeneous palladium and platinum catalysts via coating with a silicone elastomer
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We have developed a practical protocol for coating of commercial Pd/Al2O3 and Pt/Al2O3 catalysts in micro-powders with a silicone elastomer. Compared to original catalysts, the treated catalysts are easier to weight and transfer, and they are easier to recover by simple filtration. More importantly, the metal leaching of treated catalysts was significantly reduced. The treated catalysts worked very well in diverse hydrogenation reactions.
- Zhou, Mi,Li, Tingting,Xu, Bo
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supporting information
p. 948 - 952
(2019/03/08)
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- Discovery of a Membrane-Active, Ring-Modified Histidine Containing Ultrashort Amphiphilic Peptide That Exhibits Potent Inhibition of Cryptococcus neoformans
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The new structural classes of ultrashort peptides that exhibit potent microbicidal action have potential as future drugs. Herein, we report that C-2 arylated histidines containing tripeptides His(2-Ar)-Trp-His(2-Ar) exhibit potent antifungal activity against Cryptococcus neoformans with high selectivity. The most potent peptide 12f [His(2-biphenyl)-Trp-His(2-biphenyl)] displayed high in vitro activity against C. neoformans (IC50 = 0.35 μg/mL, MIC = MFC = 0.63 μg/mL) with a selectivity index of >28 and 2 times higher potency compared to amphotericin B. Peptide 12f exhibited proteolytic stability, with no apparent hemolytic activity. The mechanism of action study of 12f by confocal laser scanning microscopy and electron microscopy indicates nuclear fragmentation and membrane disruption of C. neoformans cells. Combinations of 12f with fluconazole and amphotericin B at subinhibitory concentration were synergistic against C. neoformans. This study suggests that 12f is a new structural class of amphiphilic peptide with rapid fungicidal activity caused by C. neoformans.
- Sharma, Krishna K.,Maurya, Indresh Kumar,Khan, Shabana I.,Jacob, Melissa R.,Kumar, Vinod,Tikoo, Kulbhushan,Jain, Rahul
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p. 6607 - 6621
(2017/08/17)
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- Alkylated histidine based short cationic antifungal peptides: Synthesis, biological evaluation and mechanistic investigations
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Current clinically used antifungal agents suffer from several drawbacks that have urgently necessitated the development of new antifungal agents with unusual mechanisms of action. In this context, antifungal peptides (AFPs) open up new perspectives in drug design by providing an entire range of highly selective and nontoxic pharmaceuticals. Here, we report the development of novel short AFPs with the synthesis of two series of tripeptide based compounds named as His(2-alkyl)-Arg-Lys (series I) and His(2-alkyl)-Arg-Arg (series II). The series II peptides were found to be selectively active against Cryptococcus neoformans whereas some peptides displayed encouraging activities against other fungal strains such as Candida albicans, Candida kyfer, Aspergillus Niger and Neurospora crassa. The cytotoxic experiments were performed on active compounds using Hek-293 and HeLa cells which exhibited negligible cytotoxic effect up to the highest test concentration. Further, the most potent peptide was subjected to mechanistic studies using TEM analysis. Two sets of SUVs mimicking microbial membrane and mammalian membrane were treated with the most potent peptide. The results of this study were found to be perfectly in corroboration with the antifungal activity in relation to the differences between microbial and mammalian cell membrane composition, thereby, indicating that the reported peptides may also be less susceptible to the common mechanisms of drug resistance.
- Mittal, Sherry,Kaur, Sarabjit,Swami, Anuradha,Maurya, Indresh K.,Jain, Rahul,Wangoo, Nishima,Sharma, Rohit K.
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p. 41951 - 41961
(2016/05/19)
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- Synthesis and antimicrobial activities of His(2-aryl)-Arg and Trp-His(2-aryl) classes of dipeptidomimetics
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In this communication, we report the design, synthesis and in vitro antimicrobial activity of ultra short peptidomimetics. Besides producing promising antibacterial activities against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA), the dipeptidomimetics exhibited high antifungal activity against C. neoformans with IC50 values in the range of 0.16-19 μg mL-1. The most potent analogs exhibited 4-fold higher activity than the currently used drug amphotericin B, with no apparent cytotoxicity in a panel of mammalian cell lines. This journal is the Partner Organisations 2014.
- Mahindra, Amit,Sharma, Krishna K.,Rathore, Dinesh,Khan, Shabana. I.,Jacob, Melissa R.,Jain, Rahul
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supporting information
p. 671 - 676
(2014/05/06)
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- Synthetically modified l-histidine-rich peptidomimetics exhibit potent activity against Cryptococcus neoformans
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We describe the synthesis and antimicrobial evaluation of structurally new peptidomimetics, rich in synthetically modified l-histidine. Two series of tripeptidomimetics were synthesized by varying lipophilicity at the C-2 position of l-histidine and at the N- and C-terminus. The data indicates that peptides (5f, 6f, 9f and 10f) possessing highly lipophilic adamantan-1-yl group displayed strong inhibition of Cryptococcus neoformans. Peptide 6f is the most potent of all with IC50 and MFC values of 0.60 and 0.63 μg/mL, respectively, compared to the commercial drug amphotericin B (IC50 = 0.69 and MFC = 1.25 μg/mL). The selectivity of these peptides to microbial pathogen was examined by a tryptophan fluorescence quenching study and transmission electron microscopy. These studies indicate that the peptides plausibly interact with the mimic membrane of pathogen by direct insertion, and results in disruption of membrane of pathogen.
- Jain, Rahul,Mahindra, Amit,Bagra, Nitin,Wangoo, Nishima,Jain, Rohan,Khan, Shabana I.,Jacob, Melissa R.
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p. 3150 - 3154
(2014/06/24)
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- Synthetically modified l-histidine-rich peptidomimetics exhibit potent activity against Cryptococcus neoformans
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We describe the synthesis and antimicrobial evaluation of structurally new peptidomimetics, rich in synthetically modified l-histidine. Two series of tripeptidomimetics were synthesized by varying lipophilicity at the C-2 position of l-histidine and at the N- and C-terminus. The data indicates that peptides (5f, 6f, 9f and 10f) possessing highly lipophilic adamantan-1-yl group displayed strong inhibition of Cryptococcus neoformans. Peptide 6f is the most potent of all with IC50 and MFC values of 0.60 and 0.63 μg/mL, respectively, compared to the commercial drug amphotericin B (IC50 = 0.69 and MFC = 1.25 μg/mL). The selectivity of these peptides to microbial pathogen was examined by a tryptophan fluorescence quenching study and transmission electron microscopy. These studies indicate that the peptides plausibly interact with the mimic membrane of pathogen by direct insertion, and results in disruption of membrane of pathogen.
- Mahindra, Amit,Bagra, Nitin,Wangoo, Nishima,Jain, Rohan,Khan, Shabana I.,Jacob, Melissa R.,Jain, Rahul
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p. 3150 - 3154
(2015/02/19)
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- Magnesium/hydrazinium monoformate: A new hydrogenation method for removal of some commonly used protecting groups in peptide synthesis
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Removal of some commonly used protecting groups in peptide synthesis by catalytic transfer hydrogenation employing hydrazinium monoformate and magnesium is described. This method is equally competitive with other methods in deblocking most of the commonly used protecting groups in peptide synthesis. tert-Butyl derived and base labile protecting groups were completely stable under these conditions. The use of Mg/NH2-NH2·HCOOH makes this a rapid, low-cost alternative to palladium and reduces the work-up to a simple and extraction operation.
- Channe Gowda
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p. 311 - 313
(2007/10/03)
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- ONE-POT N-PROTECTION OF AMINO ACIDS
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Attention is called on the extreme simple procedure for N-protection of amino acids mediated through previous silylation.Although the methodology is known, it has rather scarcely been used.Some examples show the versatility of a one-pot procedure.Selective Boc and Z- Nα-protections of His were also worked out.
- Becu, Chr.,Reyniers, M.-F.,Anteunis, M. J. O.,Callens, R.
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p. 779 - 782
(2007/10/02)
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- 4-Methoxy-2,3,6-trimethylbenzenesulfonyl (Mtr): a New Amino and Imidazole Protecting Group in Peptide Synthesis
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The 4-methoxy-2,3,6-trimethylbenzenesulfonyl (Mtr) group was introduced as a protecting group for the amino function, especially the ε-amino function of lysine, and the imidazole ring of histidine.The Nε-Mtr group was removable by dilute methanesulfonic acid-containing trifluoroacetic acid-thioanisole, but was stable to trifluoroacetic acid or catalytic hydrogenation.The Nim-Mtr group was removable by trifluoroacetic acid-dimethylsulfide or 1-hydroxybenzotriazole, but was more stable than the Nim-Tos or the Nim-Mbs group with triethylamine.To examine the usefulness of the Mtr group as a protecting group for use in peptide synthesis, mastoparan X and chicken gastrin releasing peptide (c-GRP) were synthesized, and this group was found to be very convenient for general solution synthesis.In particular, the introduction of Lys(Mtr) made possible a new strategy in peptide synthesis.Keywords-4-methoxy-2,3,6-trimethylbenzenesulfonyl (Mtr); Nε-4-methoxy-2,3,6-trimethylbenzenesulfonyllysine; Nim-4-methoxy-2,3,6-trimethylbenzenesulfonylhistidine; methanesulfonic acid-trifluoroacetic acid-thioanisole deprotection; trifluoroacetic acid-dimethylsulfide deprotection; mastoparan X; chicken gastrin releasing peptide
- Wakimasu, Mitsuhiro,Kitada, Chieko,Fujino, Masahiko
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p. 2766 - 2779
(2007/10/02)
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- IMPROVED METHODS OF OBTAINING Nim-TRITYL-SUBSTITUTED HISTIDINE DERIVATIVES
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Two variants are proposed for the synthesis of Nα-Boc-Nim-tritylhistidiine.The first variant starts from Nα,Nim-di-Boc-histidine, from which the Nim-Boc group is removed with hydrazine hydrate.The Nα-Boc-histidine formed is esterified with chlorotrimethylsilane, tritylated in the imidazole group, and, after the elimination of the trimethylsilyl protection from the carboxyl group, Nα-Boc-Nim-tritylglycine is obtained with a yield of 80percent.The second variant starts from Nα,Nim-ditritylhistidine, which, by treatment with hydrochloric acid in acetone and then with dilute ammonia, is converted into Nim- tritylhistidine.From this, by acylation with di-tert-butyl pyrocarbonate, Nα-Boc-Nim-tritylhistidine is obtained with a yield of 91percent.The acylation of Nim-tritylhistidine with other alkoxycarbonylating reagents leads to Nα-tert-amyl-, Nα-benzyl-, and Nα-4-methoxybenzyloxycarbonyl derivatives of Nim-tritylhistidine.
- Pozdnev, V. F.
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p. 322 - 327
(2007/10/02)
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- CLEAVAGE OF PEPTIDE TO SPARROW-RESIN BOND BY CATALYTIC TRANSFER HYDROGENOLYSIS WITH 1,4-CYCLOHEXADIENE
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Cleavage of benzyl ester-type linkage to the Sparrow modified polystyrene support was attempted with the aid of catalytic transfer hydrogenation using 1,4-cyclohexadiene and palladium black, and satisfactory yields were obtained.This will provide an alternatively efficient and mild method for the final deblocking step during improved solid phase peptide synthesis.
- Colombo, Roberto
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p. 1119 - 1122
(2007/10/02)
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