13734-28-6Relevant articles and documents
Examination of N-hydroxylation as a prerequisite mechanism of nitric oxide synthase inactivation
Maurer, Tristan S.,Pan, Jianping,Booth, Brian P.,Kalman, Thomas I.,Fung, Ho-Leung
, p. 1077 - 1080 (2000)
L-N5-(1-Hydroxyiminoethyl)-ornithine (L-NHIO) and L-N6-(1-hydroxyiminoethyl)-lysine (L-NHIL) were synthesized and tested as potential intermediates in the mechanism-based inactivation of nitric oxide synthase (NOS) by L-N5-iminoethyl-ornithine (L-NIO) and L-N6-iminoethyllysine (L-NIL). Although these compounds were determined to be competitive inhibitors, mechanism-based inactivation was not observed. (C) 2000 Elsevier Science Ltd. All rights reserved.
An affinity-based probe for the proteomic profiling of aspartic proteases
Chattopadhaya, Souvik,Chan, Elaine W. S.,Yao, Shao Q.
, p. 4053 - 4056 (2005)
We have developed an affinity-based probe for the proteomic profiling of aspartic proteases. Our probe was shown to be selective towards aspartic proteases over other proteins. It was also shown that the strategy may be used to label selectively aspartic proteases in the presence of a large excess of other proteins, thus making it useful for future proteome profiling experiments.
The microenvironment and pKaperturbation of aminoacyl-tRNA guided the selection of cationic amino acids
Hazra, Bibhas,Prasad, Mahesh,Roy, Rajat,Tarafdar, Pradip K.
supporting information, p. 8049 - 8056 (2021/10/04)
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.
COMPOUND COMPRISING A NUCLEIC ACID AND A HALF-LIFE EXTENSION MOTIF
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Paragraph 0758, (2021/06/04)
Disclosed herein are compounds including a nucleic acid (A), their preparation, and their use.
A GENETICALLY ENCODED, PHAGE-DISPLAYED CYCLIC PEPTIDE LIBRARY AND METHODS OF MAKING THE SAME
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Paragraph 0094; 00111; 00172-00173, (2020/12/07)
Embodiments of the present disclosure pertain to methods of selecting cyclic peptides that bind to a target by transforming a phage display library with a plurality of nucleic acids into bacterial host cells, where the nucleic acids include phage coat protein genes with a combinatorial region that encodes at least one cysteine and at least one non-canonical amino acid. The transformation results in the production of phage particles with phage coat proteins where the cysteine and the non-canonical amino acid couple to one another to form a cyclic peptide library. Phage particles are then screened against the desired target to select bound cyclic peptides. Amino acid sequences of the selected cyclic peptides are then identified. Additional embodiments pertain to methods of constructing a phage display library that encodes the cyclic peptides. Further embodiments of the present disclosure pertain to the produced cyclic peptides, phage display libraries and phage particles.
Two Distinct Mechanisms for C-C Desaturation by Iron(II)- and 2-(Oxo)glutarate-Dependent Oxygenases: Importance of α-Heteroatom Assistance
Dunham, Noah P.,Chang, Wei-Chen,Mitchell, Andrew J.,Martinie, Ryan J.,Zhang, Bo,Bergman, Jonathan A.,Rajakovich, Lauren J.,Wang, Bo,Silakov, Alexey,Krebs, Carsten,Boal, Amie K.,Bollinger, J. Martin
, p. 7116 - 7126 (2018/05/15)
Hydroxylation of aliphatic carbons by nonheme Fe(IV)-oxo (ferryl) complexes proceeds by hydrogen-atom (H?) transfer (HAT) to the ferryl and subsequent coupling between the carbon radical and Fe(III)-coordinated oxygen (termed rebound). Enzymes that use H?-abstracting ferryl complexes for other transformations must either suppress rebound or further process hydroxylated intermediates. For olefin-installing C-C desaturations, it has been proposed that a second HAT to the Fe(III)-OH complex from the carbon α to the radical preempts rebound. Deuterium (2H) at the second site should slow this step, potentially making rebound competitive. Desaturations mediated by two related l-arginine-modifying iron(II)- and 2-(oxo)glutarate-dependent (Fe/2OG) oxygenases behave oppositely in this key test, implicating different mechanisms. NapI, the l-Arg 4,5-desaturase from the naphthyridinomycin biosynthetic pathway, abstracts H? first from C5 but hydroxylates this site (leading to guanidine release) to the same modest extent whether C4 harbors 1H or 2H. By contrast, an unexpected 3,4-desaturation of l-homoarginine (l-hArg) by VioC, the l-Arg 3-hydroxylase from the viomycin biosynthetic pathway, is markedly disfavored relative to C4 hydroxylation when C3 (the second hydrogen donor) harbors 2H. Anchimeric assistance by N6 permits removal of the C4-H as a proton in the NapI reaction, but, with no such assistance possible in the VioC desaturation, a second HAT step (from C3) is required. The close proximity (≤3.5 ?) of both l-hArg carbons to the oxygen ligand in an X-ray crystal structure of VioC harboring a vanadium-based ferryl mimic supports and rationalizes the sequential-HAT mechanism. The results suggest that, although the sequential-HAT mechanism is feasible, its geometric requirements may make competing hydroxylation unavoidable, thus explaining the presence of α-heteroatoms in nearly all native substrates for Fe/2OG desaturases.
An Allyl Protection and Improved Purification Strategy Enables the Synthesis of Functionalized Phosphonamidate Peptides
Cramer, Jonathan,Klebe, Gerhard
supporting information, p. 1857 - 1866 (2017/04/06)
For modern biophysical methods such as isothermal titration calorimetry, high purity of the inhibitor of interest is indispensable. Herein, we describe a procedure for the synthesis and purification of functionalized phosphonamidate peptides that is able to generate inhibitors for the metalloprotease thermolysin for use in biophysical experiments. The method utilizes an allyl ester/alloc protection strategy and takes advantage of a fast and effective solid-phase extraction (SPE) purification step. Applying this strategy, we were able to synthesize a series of highly polar inhibitors featuring amino- and hydroxy-functionalized side chains in excellent purity.
Paliperidone amino acid ester and its preparation method
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Paragraph 0050; 0051; 0052, (2017/01/12)
The invention discloses a preparation method of a paliperidone amino-acid ester compound or medicinal salt thereof used for treating mental disease, wherein the structural formula of the compound is shown as a formula (I) (described in the specification). The compound can be an optical isomer and also can be a racemic mixture. The paliperidone amino-acid ester can be metabolized and converted into paliperidone (II) with pharmacological activity in vivo after being ingested in a human body, the paliperidone (II) is taken as an antagonist for neurotransmission substance to play a pesticide effect, and the paliperidone (II) is used for treating related mental diseases such as schizophrenia.
A kind of amino acid- the amine decorates composition and its preparation method and application
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Paragraph 0058; 0059; 0062, (2017/04/05)
The invention belongs to the field of medicinal chemistry and in particular relates to amino acid-amine conjugate and a preparation method and application thereof. A general formula of the amino acid-amine conjugate is shown in the specification. According to the amino acid-amine conjugate, amino acid and amine are combined together, the water solubility, biological properties and drug targeting of amine compounds can be improved, and anti-cancer targeting can be realized.
A diversity-oriented synthesis strategy enabling the combinatorial-type variation of macrocyclic peptidomimetic scaffolds
Isidro-Llobet, Albert,Hadje Georgiou, Kathy,Galloway, Warren R. J. D.,Giacomini, Elisa,Hansen, Mette R.,Méndez-Abt, Gabriela,Tan, Yaw Sing,Carro, Laura,Sore, Hannah F.,Spring, David R.
supporting information, p. 4570 - 4580 (2015/04/14)
Macrocyclic peptidomimetics are associated with a broad range of biological activities. However, despite such potentially valuable properties, the macrocyclic peptidomimetic structural class is generally considered as being poorly explored within drug discovery. This has been attributed to the lack of general methods for producing collections of macrocyclic peptidomimetics with high levels of structural, and thus shape, diversity. In particular, there is a lack of scaffold diversity in current macrocyclic peptidomimetic libraries; indeed, the efficient construction of diverse molecular scaffolds presents a formidable general challenge to the synthetic chemist. Herein we describe a new, advanced strategy for the diversity-oriented synthesis (DOS) of macrocyclic peptidomimetics that enables the combinatorial variation of molecular scaffolds (core macrocyclic ring architectures). The generality and robustness of this DOS strategy is demonstrated by the step-efficient synthesis of a structurally diverse library of over 200 macrocyclic peptidomimetic compounds, each based around a distinct molecular scaffold and isolated in milligram quantities, from readily available building-blocks. To the best of our knowledge this represents an unprecedented level of scaffold diversity in a synthetically derived library of macrocyclic peptidomimetics. Cheminformatic analysis indicated that the library compounds access regions of chemical space that are distinct from those addressed by top-selling brand-name drugs and macrocyclic natural products, illustrating the value of our DOS approach to sample regions of chemical space underexploited in current drug discovery efforts. An analysis of three-dimensional molecular shapes illustrated that the DOS library has a relatively high level of shape diversity.
