- Structural design and synthesis of bimodal PNA that simultaneously binds two complementary DNAs to Form fused double duplexes
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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.
- Gupta, Manoj Kumar,Madhanagopal, Bharath Raj,Datta, Dhrubajyoti,Ganesh, Krishna N.
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- Peptide Nucleic Acid with Double Face: Homothymine-Homocytosine Bimodal Cα-PNA (bm-Cα-PNA) Forms a Double Duplex of the bm-PNA2:DNA Triplex
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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.
- Gupta, Manoj Kumar,Madhanagopal, Bharath Raj,Ganesh, Krishna N.
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- A PROCESS FOR THE PREPARATION OF L-GLUTAMINE
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The present invention relates to a process for the preparation of L-Glutamine of Formula (I). The present invention also relates to an improved process for the purification of L-Glutamine of Formula (I) having specific bulk density and Hausner ratio.
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Page/Page column 13; 14; 15
(2022/01/24)
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- Cγ(S/ R)-Bimodal Peptide Nucleic Acids (Cγ- bm-PNA) Form Coupled Double Duplexes by Synchronous Binding to Two Complementary DNA Strands
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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.
- Bhingardeve, Pramod,Madhanagopal, Bharath Raj,Ganesh, Krishna N.
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supporting information
p. 13680 - 13693
(2020/12/15)
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- Preparation method of 3-amino-2,6-piperidinedione hydrochloride
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The invention discloses a preparation method of 3-amino-2,6-piperidinedione hydrochloride. The method comprises the following steps that (1) L-glutamine is protected in an alkaline medium to obtain N-tert-butyl oxyformyl-L-glutamine; (2) under the anhydrous condition, the N-tert-butyl oxyformyl-L-glutamine obtained in step (1) and N,N-carbonyldiimidazole are subjected to cyclization under catalysis of 4-dimethylamino pyridine to obtain N-tert-butyl oxyformyl-3-amino-2,6-piperidinedione; (3) the N-tert-butyl oxyformyl-3-amino-2,6-piperidinedione obtained in step (2) is subjected to deprotectionin an acid medium, hydrochloride is formed, and the 3-amino-2,6-piperidinedione hydrochloride is obtained. The target product, namely the 3-amino-2,6-piperidinedione hydrochloride, is obtained by three steps including protection, cyclization, deprotection and hydrochloride forming, and the obtained product is high in purity and stable in quality. According to the preparation method, only three steps are needed in the synthesis process, the path is simple, the reaction conditions are mild, a high-pressure hydrogenation condition is not needed, the cost is low, and industrialization is easy toachieve.
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Paragraph 0032; 0034; 0035; 0041-0072
(2019/02/19)
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- Preparation method of L-2,4-diaminobutyrate hydrochloride
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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.
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Paragraph 0020-0023
(2019/10/22)
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- (S)-2-methyl-1,4,5,6-tetrahydromethylpyrimidine-4-carboxylic acid synthesis method
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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.
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Paragraph 0047; 0048; 0049; 0075; 0076
(2017/08/30)
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- CATIONIC LIPID CORDIARIMIDE HYBRID COMPOUNDS AND A PROCESS FOR PREPARATION THEREOF
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The present invention relates to the cationic lipid cordiaroimide hybrid compounds of formula I. The present invention provides a process for preparation of these compounds is also being elaborated. The compounds described provides anticancerous activity against cell lines including PC-3 (prostate cancer), HepG2 (liver cancer), MCF-7 (breast cancer) and NIH/3T3 (non cancer) cells. The compound was also capable of inducing caspase-3 mediated apoptosis in HepG2 cells by arresting the cell cycle in the G1 phase. Furthermore, the compound exhibited DNA ligase I inhibition. The present class of cationic lipid cordiarimide hybrids is likely to find specific use in developing novel targeted therapies for liver and prostate cancers.
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Page/Page column 14
(2016/01/01)
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- Design, synthesis and primary activity of thiomorpholine derivatives as DPP-IV inhibitors
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Thirteen thiomorpholine-bearing compounds were designed and synthesized as dipeptidyl peptidase IV (DPP-IV) inhibitors, with natural and non-natural l-amino acids as the starting materials. Their structures were characterized by 1H NMR, 13C NMR and HR-MS. The target compounds were screened for the DPP-IV inhibition, and the preliminary SAR result was obtained. Particularly, compounds 4c, 4d and 4f with good DPP-IV inhibition in vitro were further evaluated through a mouse oral glucose tolerance test (OGTT). The preliminary result showed the potential value for further studies on those thiomorpholine-bearing compounds as DPP-IV inhibitors.
- Han, Bei,Liu, Jing Long,Huan, Yi,Li, Peng,Wu, Qi,Lin, Zi Yun,Shen, Zhu Fang,Yin, Da Li,Huang, Hai Hong
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scheme or table
p. 297 - 300
(2012/05/20)
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- Concise and efficient synthesis of highly potent and selective dipeptidyl peptidase II inhibitors
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Highly potent and selective DPP II inhibitors N'-(4-Chlorobenzyl)-N'- methyl-4-oxo-4-(1-piperidinyl)-1,3-(S)-butane-diamine dihydrochloride 1 and N'-(4-chlorobenzyl)-4-oxo-4-(1-piperidinyl)-1,3-(S)-butanediamine dihydrochloride 2 have been efficiently synthesized starting from L-glutamine. A short and high yielding route with simple isolation techniques has been disclosed. Copyright Taylor & Francis Group, LLC.
- Rasheed, Abdul M.,Namala, Rambabu,Manne, Narendra,Vanjivaka, Sreelatha,Dhamjewar, Ravi,Balasubramanian, Gopalan
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p. 162 - 169
(2008/03/17)
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- Novel 3-phenylpropane-1,2-diamine derivates as inhibitors of aminopeptidase N (APN)
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Aminopeptidase N (APN) is an essential peptidase involved in the process of tumor invasion and metastasis. Here we describe a novel class of inhibitor with 3-phenylpropane-1,2-diamine as scaffold to APN. Preliminary activity evaluation with enzyme inhibition studies showed that compound 12i exhibited potent and selective inhibitory activity towards APN with the IC50 value 15.5 ± 1.2 μM.
- Shang, Luqing,Wang, Qiang,Fang, Hao,Mu, Jiajia,Wang, Xuejian,Yuan, Yumei,Wang, Binghe,Xu, Wenfang
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scheme or table
p. 9984 - 9990
(2009/04/06)
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- D-amino acid specific proteases and native all-L-proteins: A convenient combination for semisynthesis
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(Figure Presented) Side reactions side-stepped: A D-amino acid specific protease was used for the first time in the chemoenzymatic synthesis of a native protein, the peptidyl prolyl cis/trans isomerase parvulin 10 from E. coli (see scheme). Side reactions that complicate synthesis with L-amino acid specific enzymes are avoided in this approach.
- Wehofsky, Nicole,Pech, Andreas,Liebscher, Sandra,Schmidt, Stephanie,Komeda, Hidenobu,Asano, Yasuhisa,Bordusa, Frank
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supporting information; experimental part
p. 5456 - 5460
(2009/03/12)
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- New reaction conditions using trifluoroethanol for the E-I Hofmann rearrangement
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The Hofmann rearrangement of -protected glutamine esters to N2-protected (2S)-4-[(2,2,2-trifluoroethoxy)carbonyIamino]-2-aminobutyric acid esters was successfully achieved by an electrochemical method using a trifluoroethanol (TFE)-MeCN solvent system where the TFE may play an important role in controlling the basicity caused by electrochemically generated bases.
- Matsumura, Yoshihiro,Yuki Satoh, Kimihiro Shirai,Onomura, Osamu,Toshihide, Maki
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p. 2057 - 2060
(2007/10/03)
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- Fragrance precursor compounds for preventing human malodor
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The invention relates to agents preventing (the formation of) human malodor. In particular, the invention relates to the use of several classes of compounds which can act as such agents in cosmetic products, such as deodorants and antiperspirants. These compounds are normally odorless or nearly so, but upon contacting the skin as for example, in skin care compositions or in personal care compositions, they prevent malodor. The compounds under consideration are compounds of the formula The definition of the substituents is given in the specification.
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- Stable polypeptides having c-AMP production enhancing activity and the use thereof
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Disclosed are (1) a polypeptide represented by formula (I), or a pharmaceutically acceptable amide, ester or salt thereof: wherein X is hydrogen atom; or a lower alkyl group which may be substituted with a member selected from the group consisting of hydroxy group, substituted or unsubstituted amino group, carboxyl group, carbamoyl group, and substituted or unsubstituted aromatic group; and Y is one of amino acids or peptides consisting of 1 to 16 amino acid residues counted from the N-terminal side of Leu-Ala-Ala-Val-Leu-Gly-Lys-Arg-Tyr-Lys-Gln-Arg-Val-Lys-Asn-Lys SEQ ID NO: 20, and (2) a pharmaceutical composition comprising a polypeptide represented by formula (I), or a pharmaceutically acceptable amide, ester or salt thereof, which has remarkable c-AMP activity and is useful as a nerve activating agent.
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- A study of the delivery-targeting concept applied to antineoplastic drugs active on human osteosarcoma. I. Synthesis and biological activity in nude mice carrying human osteosarcoma xenografts of gem-bisphosphonic methotrexate analogues
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With the aim of verifying the concept of osteotic vectorisation, synthesis of three methotrexate (MTX) gem-diphosphonic analogues (compounds A, B and C) was performed. These molecules were tested on BALB/c and NIH III mice previously grafted with subcutaneous implants of OHS, TTX p7 and/or TTX p11 human osteosarcoma cell lines. Antineoplasic activity of compound B and C (active compounds) was compared to the activity for MTX alone and to activity of compound A (inactive compound). Compounds B and C exhibited an increased antineoplasic activity compared to MTX alone and to compound A. At equimolar doses, compound B was found to be 5-6-fold more active than MTX given alone. We have discussed the concept of osteotic vectorisation of compound B, which could be regarded as a prodrug.
- Sturtz,Appere,Breistol,Fodstad,Schwartsmann,Hendriks
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p. 825 - 833
(2007/10/02)
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- Alkylated hormone-releasing peptides and method of treatig mammals therewith
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This invention provides novel growth hormone-releasing peptides and a method for increasing the release and raising the levels of growth hormone in mammals. The invention also provides a method for increasing the growth rate of meat producing animals, treating the symptoms of growth hormone deficiencies in mammals and improving the efficiency of feed utilization by meat producing and dairy animals.
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- HIV related peptides
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Fragments of HIV p17 protein ranging in length from about 12 to abut 40 amino acids are used to form diagnostics and vaccines for detection or treatment of AIDS. Specific peptide fragments extend from the N-terminal to the C-terminal. Peptides having the amino acid sequences shown by the following formula (I), (II), (III), (IV) and (V):, Tyr-Ser-Val-His-Gln-Arg-Ile-Asp-Val-Lys--Asp-Thr-Lys-Glu-Ala-Leu-Gly-Lys-Ile-Glu--Glu-Glu-Gln-Asn-Lys-Ser-Lys-Lys-Lys-Ala (I), Gly-Ala-Arg-Ala-Ser-Val-Leu-Ser-Gly-Gly--Glu-Leu-Asp-Arg-Trp-Glu-Lys-Ile-Arg-Leu--Arg-Pro-Gly-Gly-Lys-Lys-Lys-Tyr-Lys-Leu--Lys-His (II), Ile-Val-Trp-Ala-Ser-Arg-Glu-Leu-Glu-Arg--Phe-Ala-Val-Asn-Pro-Gly-Leu-Leu (III), Glu-Thr-Ser-Glu-Gly-Cys-Arg-Gln-Ile-Leu--Gly-Gln-Leu-Gln-Pro-Ser-Leu-Gln-Thr-Gly--Ser-Glu-Glu-Leu-Arg-Ser-Leu-Tyr-Asn-Thr--Val-Ala-Thr-Leu (IV), Ala-Gln-Gln-Ala-Ala-Ala-Asp-Thr-Gly-His--Ser-Ser-Gln-Val-Ser-Gln-Asn-Tyr (V), are immunoreactive to antibodies in sera of patients testing seropositive for p17 of HIV-1.
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- PROPERTIES OF Nα,Nca-DI-TERT-BUTYLOXYCARBONYL-ω-CARBAMOYL-α-AMINO ACIDS AND DIRECT SYNTHESIS OF PROTECTED HOMOGLUTAMIC ACID DERIVATIVES
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The protected carboxamide function of Nα,Nca-di-tert-butyloxy-carbonyl-ω-carbamoyl-α-amino acids worked well with nucleophilic reagents.Applying this novel reactivity, we developed an efficient synthetic route to Nα-tert-butyloxycarbonylhomoglutamic acid and its derivatives, including Nα-tert-butyloxycarbonylhomoglutamic acid δ-benzyl ester, from Nα,Nca-di-tert-butyloxycarbonylhomoglutamine.KEYWORDS - protected homoglutamic acid synthesis; Nca-tert-butyloxycarbonylated carboxamide; hydrolysis; selective deprotection; Nα-tert-butyloxycarbonylhomoglutamic acid δ-benzyl ester; Nα-tert-butyloxycarbonylhomoglutamic acid α-tert-butyl ester; Nα-tert-butyloxycarbonylhomoglutamine; optical purity
- Sakura, Naoki,Hirose, Kyoko,Hashimoto, Tadashi
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p. 3506 - 3509
(2007/10/02)
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- Synthesis of a proposed antigenic hexapeptide from Escherichia coli K88 protein fimbriae.
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The hexapeptide Boc-Asp-Asp-Tyr-Arg-Gln-Lys-OMe is assembled by stepwise synthesis in solution with an overall yield of 44%. N alpha-boc-amino acids, protected with benzyl or benzyloxycarbonyl groups in the side-chains, are coupled as active estes of 1-hydroxybenzotriazole in mixtures of dichloromethane and N,N-dimethylformamide. N alpha-deprotection is accomplished with trifluoroacetic acid. Finally, hydrogenation with palladium on charcoal and ammonium formate produces the pure hexapeptide. A new one-pot synthesis of Boc-Arg(Z2) is described, and the use of this derivative in peptide coupling is studied. The synthetic peptide was coupled to BSA and used in direct immunication of rabbits.
- Meldal,Kindtler
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p. 235 - 241
(2007/10/02)
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- Untriakontapeptide with opiate activity
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An untriakontapeptide having significant opiate agonist activity has been isolated from camel pituitary glands. The structure of this peptide has been determined and this peptide was then synthesized utilizing solid phase peptide synthesis. Both natural and synthetic material show identical physical and biological properties.
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