80445-78-9Relevant articles and documents
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.
Peptide Nucleic Acid with Double Face: Homothymine-Homocytosine Bimodal Cα-PNA (bm-Cα-PNA) Forms a Double Duplex of the bm-PNA2:DNA Triplex
Gupta, Manoj Kumar,Madhanagopal, Bharath Raj,Ganesh, Krishna N.
, p. 414 - 428 (2020/12/22)
Cα-bimodal peptide nucleic acids (bm-Cα-PNA) are PNAs with two faces and are designed homologues of PNAs in which each aminoethylglycine (aeg) repeating unit in the standard PNA backbone hosts a second nucleobase at Cα through a spacer chain with a triazole linker. Such bm-Cα-PNA with mixed sequences can form double duplexes by simultaneous binding to two complementary DNAs, one to the base sequence on t-amide side and the other to the bases on the Cα side chain. The synthesis of bm-Cα-PNA with homothymine (T7) on the t-amide face and homocytosine (C5) on the Cα side chain through the triazole linker was achieved by solid phase synthesis with the global click reaction. In the presence of complementary DNAs dA8 and dG6 at neutral pH, bm-Cα-PNA 1 forms a higher order pentameric double duplex of a triplex composed of two bm-Cα-PNA-C5:dG5 duplexes built on a core (bm-Cα-PNA-T7)2:dA8 triplex. Circular dichroism studies showed that assembly can be achieved by either triplex first and duplex later or vice versa. Isothermal titration calorimetry data indicated that the assembly is driven by favorable enthalpy. These results validate concurrent multiple complex formation by bimodal PNAs with additional nucleobases at Cα or Cγon the aeg-PNA backbone and open up ways to design programmed supramolecular assemblies.
Synthesis method of 2,4-diaminobutyric acid derivative
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Paragraph 0086-0089, (2021/03/11)
The invention belongs to the field of organic chemistry, and particularly relates to a synthesis method of a 2,4-diaminobutyric acid derivative. According to the synthesis method of the 2,4-diaminobutyric acid and the derivative thereof provided by the invention, homoserine is selected as an initial raw material, the amino and carboxyl of the homoserine are protected firstly, a pht group is introduced through a light delay reaction, and then a final product can be obtained through six steps of benzyl ester removal, pht removal and Boc group removal. According to the invention, the synthetic method provided by the invention has relatively high reaction yield and is convenient for separation and purification; the intermediates obtained in the reaction are all protecting group modified aminoacid derivatives and can be directly used as drug intermediates or raw materials for synthesizing other compounds, so that waste is avoided; and the reaction conditions provided by the invention are mild, and later-period amplification production is facilitated.
Cγ(S/ R)-Bimodal Peptide Nucleic Acids (Cγ- bm-PNA) Form Coupled Double Duplexes by Synchronous Binding to Two Complementary DNA Strands
Bhingardeve, Pramod,Madhanagopal, Bharath Raj,Ganesh, Krishna N.
, p. 13680 - 13693 (2020/12/15)
Peptide nucleic acids (PNAs) are linear equivalents of DNA with a neutral acyclic polyamide backbone that has nucleobases attached via tert-amide link on repeating units of aminoethylglycine. They bind complementary DNA or RNA with sequence specificity to form hybrids that are more stable than the corresponding DNA/RNA self-duplexes. A new type of PNA termed bimodal PNA [Cγ(S/R)-bm-PNA] is designed to have a second nucleobase attached via amide spacer to a side chain at Cγon the repeating aeg units of PNA oligomer. Cγ-bimodal PNA oligomers that have two nucleobases per aeg unit are demonstrated to concurrently bind two different complementary DNAs, to form duplexes from both tert-amide side and Cγside. In such PNA:DNA ternary complexes, the two duplexes share a common PNA backbone. The ternary DNA 1:Cγ(S/R)-bm-PNA:DNA 2 complexes exhibit better thermal stability than the isolated duplexes, and the Cγ(S)-bm-PNA duplexes are more stable than Cγ(R)-bm-PNA duplexes. Bimodal PNAs are first examples of PNA analogues that can form DNA2:PNA:DNA1 double duplexes via recognition through natural bases. The conjoined duplexes of Cγ-bimodal PNAs can be used to generate novel higher-level assemblies.
Structural design and synthesis of bimodal PNA that simultaneously binds two complementary DNAs to Form fused double duplexes
Gupta, Manoj Kumar,Madhanagopal, Bharath Raj,Datta, Dhrubajyoti,Ganesh, Krishna N.
, p. 5255 - 5260 (2020/07/16)
Bimodal PNAs are new PNA constructs designed to bind two different cDNA sequences synchronously to form double duplexes. They are synthesized on solid phase using sequential coupling and click reaction to introduce a second base in each monomer at Cα via alkyltriazole linker. The ternary bimodal PNA:DNA complexes show stability higher than that of individual duplexes. Bimodal PNAs are appropriate to create higher-order fused nucleic acid assemblies.
Preparation method of L-2,4-diaminobutyrate hydrochloride
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Paragraph 0020-0023, (2019/10/22)
The invention belongs to the technical field of organic chemistry, and discloses a preparation method of L-2,4-diaminobutyrate hydrochloride. The method includes the following steps that S1, L-glutamine is subjected to Boc protection under an alkaline condition to obtain a N-BOC-L-glutamine aqueous solution; S2, a saturated sodium hypochlorite solution is dropwise added into the N-Boc-L-glutamineaqueous solution obtained in the S1 for a degradation reaction, and a L-2-N-Boc-4-aminobutyric acid crude product solution is obtained; S3, the L-2-N-Boc-4-aminobutyric acid crude product solution iscondensed, the pH is adjusted with 2N hydrochloric acid, salt is removed with cation exchange resin, dilute ammonia water is used as an elution agent for elution, the eluent is condensed, concentratedhydrochloric acid is added for adjusting the pH of a concentrated solution, absolute ethyl alcohol is added, and after crystallization, filtering and drying, the L-2,4-diaminobutyrate hydrochloride is obtained. The method has the advantages that the synthetic route is short, operation is simple, three wastes pollution is less, the yield is high and the cost is low, and the method is an ideal scheme for industrial scale-up production.
2,4-diaminobutyric acid derivative and preparation method thereof
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Paragraph 0053; 0054; 0055, (2017/07/20)
The invention relates to a 2,4-diaminobutyric acid derivative and a preparation method thereof and relates to the field of medicine synthesis. An aspartic acid derivative serves as an initiator, and the 2,4-diaminobutyric acid derivative is obtained through simple reduction and substitution reaction. Different from the prior art, a reagent adopted for the method is small in toxicity, reaction conditions are mild, requirements for a device are not high, synthesis steps are simple, the 2,4-diaminobutyric acid derivative can be obtained at a high total yield, and the 2,4-diaminobutyric acid derivative facilitates large-scale industrial production and can be well applied to medicine synthesis.
(S)-2-methyl-1,4,5,6-tetrahydromethylpyrimidine-4-carboxylic acid synthesis method
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, (2017/08/30)
The present invention relates to a (S)-2-methyl-1,4,5,6-tetrahydromethylpyrimidine-4-carboxylic acid synthesis method. According to the method, L-glutamine is used as a raw material, the alpha-amino of the L-glutamine is protected with a protection group, a decarbonylating agent is added, a Hofmann degradation reaction is performed to remove the carbonyl group attached to the remaining amino, the protection group is removed to obtain L-2,4-diaminobutyric acid, and finally the prepared L-2,4-diaminobutyric acid and trimethyl orthoacetate are subjected to a ring forming reaction to obtain the (S)-2-methyl-1,4,5,6-tetrahydromethylpyrimidine-4-carboxylic acid. Compared to the method in the prior art, the method of the present invention has the following characteristics that the chemical synthesis route is provided, the steps of the synthesis process are simple, the raw materials are easy to obtain, the product purity is high, and the method is suitable for large-scale industrial production.
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.
SELECTIVE NAV1.7 INHIBITORS FOR THE TREATMENT OF DIABETES
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Paragraph 00383; 00384, (2016/06/01)
Provided herein are methods for treating or preventing prediabetes or diabetes, or maintaining or lowering blood or plasma glucose or maintaining or lowering blood or plasma glycated hemoglobin comprising administering to a subject in need thereof a therapeutically effective amount of a compound selectively inhibiting NaVl.7. In particular, provided herein are processes for the preparation of and intermediates used in the preparation of compounds selectively inhibiting NaV1.7, such as the compounds of Formula (I) or compounds of Formula (I').
