Refernces
10.1002/asia.201700538
The research focuses on the development of an efficient peptide synthesis approach through a one-pot aziridine-mediated ligation-desulfurization strategy, specifically targeting the incorporation of phenylalanine and tryptophan residues into α-peptides. The methodology involves the regioselective ring-opening of aziridine-3-aryl-2-carboxylates with peptide thioacids, followed by desulfurization to yield the desired peptides. Key reactants include 3-phenyl- and 3-indolyl-substituted aziridin-2-carboxylates derivatives, synthesized from (2S,3R) β-hydroxy–α-azidophenylalanine and N-protected (2S,3R) β-hydroxy–α-azidotryptophan, and various peptide thioacids such as Boc-L-Val-SH. The experiments utilized solvents like DMF, DCM, THF, and ethanol, with reagents such as NaBH4/NiCl2.6H2O for the desulfurization step. The optimization of reaction conditions was conducted to maximize yields, and the scope of the method was explored with different peptide thioacids. Analyses included TLC monitoring, 1H NMR, and LC-HRMS to characterize intermediates and final products, confirming the regioselective formation of α-peptides with phenylalanine and tryptophan.
10.1021/jo702573z
The study focuses on the synthesis and structural characterization of novel spirobarbiturates as effective β-turn mimetics, which are important for molecular recognition and signal transduction. The researchers synthesized spirobarbiturates of type III using N-carbamoyl-substituted amino acids and pyrrolidine-1,2,2-tricarboxylic acid derivatives through cyclocondensation reactions. Key chemicals used in the study included N-Boc-protected diethylaminomalonate, 1,3-dibromopropane, and various urea derivatives (e.g., N-carbamoyl glycine, phenylalanine, and tyrosine), which served as building blocks in the synthesis process. The introduction of these compounds aimed to create molecular scaffolds that could be utilized as biomolecular probes to explore binding interactions with target proteins, ultimately contributing to the development of peptide mimetics with potential therapeutic applications.
10.1016/0022-2860(91)87146-9
The research aimed to investigate the properties of aromatic residues in ferricytochrome c3, a tetrahaeme protein from Desulfovibrio vulgaris Miyazaki F, using 'H NMR spectroscopy. The study established conditions for the specific labeling of the protein during bacterial culture in a minimal medium, achieving over 85% efficiency in specifically deuterated phenylalanine and tyrosine residues. The research concluded that while the signals of one phenylalanine residue were missing, likely due to its assignment to Phe20, the aromatic proton signals of His67 were assigned through p2H titration, revealing a much higher pKa than that of free histidine residues. No tyrosine residue was found to be ionized up to p2H 12, suggesting their involvement in the protein's structure and function.
10.2174/157017809790443005
The study presents a new method for preparing N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), an irreversible serine protease inhibitor, without using toxic and explosive diazomethane. L-Phenylalanine is first tosylated to form N-tosyl-L-phenylalanine, which is then converted into its 4-nitrophenyl ester using DCC and DMAP. This ester reacts with dimethylsulfoxonium methylide, generated from trimethylsulfoxonium iodide and potassium tert-butoxide, to form a sulfur ylide. The sulfur ylide is subsequently treated with lithium chloride and methanesulfonic acid to produce the chloroketone, TPCK. This method achieves an overall yield of 36% and avoids the use of hazardous diazomethane, providing a safer and practical synthesis route.
10.1021/jm00104a004
This research investigates the development and evaluation of N-substituted peptides containing α,α-difluorostatone residues as potent inhibitors of human leukocyte elastase (HLE), a serine protease implicated in various diseases such as emphysema and arthritis. The study aims to design inhibitors that can effectively bind to HLE and inhibit its activity, potentially serving as therapeutic agents. Key chemicals used include α,α-difluorostatone derivatives of amino acids like L-valine, L-leucine, and L-phenylalanine, with the α,α-difluoromethylene ketone derivative of L-valine proving to be the most effective at the P1 position. The peptides also incorporate a nonproteinogenic residue, N-(2,3-dihydro-lH-inden-2-yl)glycine, at the P2 position, which acts as a bioisosteric replacement for L-proline. The most potent in vitro compound, 17b, has an IC50 of 0.635 μM. Extended inhibitors like 23b and 24b were designed to interact with additional binding subsites of HLE, enhancing their potency. The study concludes that these α,α-difluoromethylene ketone inhibitors effectively inhibit HLE through transition-state analog mechanisms, forming reversible hemiketals with the active site Ser195 of HLE. The inhibitors were also tested in an elastase-induced pulmonary hemorrhage model in hamsters, with 22c showing significant inhibition of hemorrhage in a dose-dependent manner. The research highlights the potential of these peptides as therapeutic agents for HLE-related diseases.
10.1039/b104137c
The research focuses on the protease-catalyzed synthesis of carbohydrate-amino acid conjugates, specifically glycopeptide analogues, through a highly regioselective and carbohydrate-specific process. The purpose of this study was to develop a ready and short route for the creation of ester-linked glycopeptides, which are known to display a wide variety of potent biological activities with potential therapeutic and commercial value. The researchers used amino acid vinyl ester acyl donors and minimally or completely unprotected carbohydrate acyl acceptors to probe the active sites of proteases. They found that the yield efficiencies were modulated by the carbohydrate C-2 substituent, which could be exploited for selective one-pot syntheses. The study successfully established a method for constructing glycan-peptide conjugates with yields ranging from 23–76%, which is comparable to or better than alternative routes employing protection-deprotection strategies. The chemicals used in the process included serine protease subtilisin Bacillus lentus (SBL) as a catalyst, and amino acids such as phenylalanine, aspartic acid, and glutamic acid, along with various carbohydrate acyl acceptors. The research concluded that the protease-catalyzed transesterification process is a powerful method for creating glycopeptides, which can be further extended at their sugar reducing end or peptide N-terminal, and that the substrate specificity of the proteases SBL and TLCLEC showed a strong preference for phenylalanine with flexibility in N-protection.
10.1016/j.bmc.2011.02.014
The researchers synthesized a series of substituted taurine sulfonyl fluorides derived from taurine or protected amino acids, using reagents such as KF/18-crown-6 and DAST for the synthesis of sulfonyl fluorides. The potency of these inhibitors was evaluated through various enzyme assays, leading to binding affinities up to 22 μM. The conclusions drawn from the study indicate that these sulfonyl fluorides are capable of irreversible competitive inhibition of serine proteases, with affinities dependent on the side chain of the inhibitor. The best binding affinity was observed for the phenylalanine-derived sulfonyl fluoride, which was comparable to the known potent inhibitor PMSF.
10.1039/P19910003117
The research investigates the N-deprotection of Z- and Boc-aminomethylene pseudodipeptide methyl esters and their subsequent cyclization to 2-ketopiperazines. The study aims to understand the factors influencing the extent of lactamization, which were found to be dependent on the nature of the amino acid, sequence order, and deprotection conditions. Key chemicals used include Z- and Boc-protected pseudodipeptides, amino acids like Leu, Lys, Arg, Phe, and Trp, and reagents such as NaBH3CN, ZnCl2, MeOH, Pd/C, HCl, trifluoroacetic acid (TFA), and N-methylmorpholine. The study concludes that lactamization occurs easily under various deprotection methods, and the resulting cyclic analogues could be valuable as building blocks in peptide-mimics research.
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