- A short, rigid linker between pyrene and guanidiniocarbonyl-pyrrole induced a new set of spectroscopic responses to the ds-DNA secondary structure
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A novel pyrene-guanidiniocarbonyl-pyrrole dye, characterised by a short, rigid linker between the two chromophores, interacts strongly with ds-DNA but only negligibly with ds-RNA. Under neutral conditions the dye shows strong selectivity toward AT-DNA (with respect to GC-DNA). Binding is accompanied by a specific ICD band at 350 nm and fluorescence quenching for all DNAs/RNAs studied. At pH 5 the affinity of the dye is reversed, now favouring GC-DNA over AT-DNA. A strong emission increase for AT-DNA is observed but with quenching for GC-DNA.
- Radi Stojkovi, Marijana,Piotrowski, Patryciusz,Schmuck, Carsten,Piantanida, Ivo
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Read Online
- LINKING AMINO ACID SEQUENCES, MANUFACTURING METHOD THEREOF, AND USE THEREOF
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This invention provides compositions comprising linked amino acid sequences, pharmaceutical compositions comprising linked amino acid sequences, and methods of making thereof. This invention also provides methods of delivering said compositions to subjects and methods of treating various disorders and diseases using the said compositions.
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- TLR2 MODULATOR COMPOUNDS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
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The present disclosure relates to compounds which modulate the activity of Toll-like receptor (TLR) proteins, including agonists or activators, partial agonists, and antagonists. Of particular interest of compounds that modulate the activity of TLR2, as well as methods of using such compounds to treat cancer and other disorders associated with a TLR2 pathway.
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Paragraph 00206-00207
(2021/12/08)
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- 2,3-Diaminopropanols obtained from D-serine as intermediates in the synthesis of protected 2,3-L-diaminopropanoic acid (L-DAP) methyl esters
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A synthetic strategy for the preparation of two orthogonally protected methyl esters of the non-proteinogenic amino acid 2,3-l-diaminopropanoic acid (l-Dap) was developed. In these structures, the base-labile protecting group 9-fluorenylmethyloxycarbonyl (Fmoc) was paired to the p-toluensulfonyl (tosyl, Ts) or acid-labile tert-butyloxycarbonyl (Boc) moieties. The synthetic approach to protected l-Dap methyl esters uses appropriately masked 2,3-diaminopropanols, which are obtained via reductive amination of an aldehyde prepared from the commercial amino acid Nα-Fmoc-O-tert-butyl-d-serine, used as the starting material. Reductive amination is carried out with primary amines and sulfonamides, and the process is assisted by the Lewis acid Ti(OiPr)4. The required carboxyl group is installed by oxidizing the alcoholic function of 2,3-diaminopropanols bearing the tosyl or benzyl protecting group on the 3-NH2 site. The procedure can easily be applied using the crude product obtained after each step, minimizing the need for chromatographic purifications. Chirality of the carbon atom of the starting d-serine template is preserved throughout all synthetic steps.
- Aiello, Donatella,Athanassopoulos, Constantinos M.,Mazzotti, Fabio,Siciliano, Carlo,Temperini, Andrea,de Luca, Pierantonio
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- A diversity-oriented synthesis strategy enabling the combinatorial-type variation of macrocyclic peptidomimetic scaffolds
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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.
- 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.
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p. 4570 - 4580
(2015/04/14)
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- A concise synthesis of the HCV protease inhibitor BILN 2061 and its P3 modified analogs
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A concise synthesis of BILN 2061 was achieved through more efficient installation of P2 4-quinoline moiety via SN2 displacement of the β-OBs group located on the 4-hydroxyl proline intermediate, which was prepared from 4-α-hydroxyl proline analog via Mitsunobu reaction with inversion of stereochemistry. In addition, a short and practical synthesis for P3 unit is also described herein. Final assembly of four fragments for BILN 2061 was achieved with an overall yield of 58% in 4 steps from P1 to 15a. Furthermore several analogs of BILN 2061 (WX-1-WX-5) containing modifications on P3 unit were synthesized successfully using the same synthetic route as described for the parent inhibitor BILN 2061. Copyright
- Liu, Dejun,Dong, Jingchao,Yin, Yunxing,Ma, Rujian,Shi, Yifeng,Wu, Hao,Chen, Shuhui,Li, Ge
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experimental part
p. 1489 - 1502
(2011/11/01)
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- Highly enantioselective synthesis of orthogonally protected (2S)-2,3-diaminopropanoates through catalytic phase-transfer aza-Henry reaction
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The syntheses of enantiomer-enriched orthogonally protected different (2S)-2,3-diaminopropanoates and unnatural furyl-substituted (tert-butoxy) carbonyl (Boc) as well as (benzyloxy)carbonyl (Cbz) protected amino acid esters are accomplished by means of an
- Kumaraswamy, Gullapalli,Pitchaiah, Arigala
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p. 1543 - 1550
(2011/10/08)
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- Iridium-catalyzed asymmetric allylic amination with polar amines: Access to building blocks with lead-like molecular properties
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The combination of an air-stable iridium catalyst and the dipolar aprotic solvent dimethyl sulfoxide (DMSO) allowed, for the first time, the systematic exploitation of highly polar, functionalized amines in asymmetric allylic substitutions: low molecular
- Tosatti, Paolo,Horn, Joachim,Campbell, Amanda J.,House, David,Nelson, Adam,Marsden, Stephen P.
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supporting information; experimental part
p. 3153 - 3157
(2011/03/18)
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- Heterocycle-amino acid derivatives for targeting cancer tissue and radioactive or non-radioactive labeled compounds thereof
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The present invention relates to novel amino acid derivatives containing heterocyclic chelating residues thereof; radioactive or nonradioactive metal complexes thereof; methods for preparation thereof; and apyrogenic and sterile preparative kits of the co
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Page/Page column 11-12
(2010/11/03)
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- Synthesis and evaluation of macrocyclic amino acid derivatives for tumor imaging by gallium-68 positron emission tomography
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68Ga PET imaging in clinical oncology represents a notable development because the availability of 68Ga is not dependent on a cyclotron. Furthermore, labeled amino acid derivatives have been proven to be useful for the imaging many t
- Shetty, Dinesh,Jeong, Jae Min,Ju, Chang Hwan,Kim, Young Ju,Lee, Ji-Youn,Lee, Yun-Sang,Lee, Dong Soo,Chung, June-Key,Lee, Myung Chul
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experimental part
p. 7338 - 7347
(2010/12/25)
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- MACROCYCLIC PEPTIDES AS HEPATITIS C VIRUS INHIBITORS
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Macrocyclic peptides having the general formula (I): are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
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Page/Page column 85-86
(2008/12/05)
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- MACROCYCLIC PEPTIDES AS HEPATITIS C VIRUS INHIBITORS
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Macrocyclic peptides having the general formula are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
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Page/Page column 82-83
(2008/12/05)
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- Hepatitis C virus inhibitors
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Hepatitis C virus inhibitors having the general formula are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
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Page/Page column 55
(2010/11/26)
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- Aziridinium from N,N-dibenzyl serine methyl ester: Synthesis of enantiomerically pure β-amino and α,β-diamino esters
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Reaction of N,N-dibenzyl-O-methylsulfonyl serine methyl ester with a variety of heteronucleophiles (sodium azide, sodium phthalimide, amines, thiols) and carbanions (sodium malonate) gave, via an aziridinium intermediate, the corresponding β-amino or α,β-
- Couturier, Cedric,Blanchet, Jerome,Schlama, Thierry,Zhu, Jieping
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p. 2183 - 2186
(2007/10/03)
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- MODULATORS OF CELLULAR ADHESION
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The present invention provides compounds having formula (I): and pharmaceutically acceptable derivatives thereof, wherein R1-R4, n, p, A, B, D, E, L and AR1 are as described generally and in classes and subclasses herein, and additionally provides pharmaceutical compositions thereof, and methods for the use thereof for the treatment of disorders mediated by the CD11/CD18 family of cellular adhesion molecules (e.g., LFA-1).
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Page/Page column 77; 79
(2010/02/11)
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- An Efficient Synthesis of a Probe for Protein Function: 2,3-Diaminopropionic Acid with Orthogonal Protecting Groups
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(Matrix presented) An efficient and cost-effective synthesis of N(α)-Boc2-N(β)-Cbz-2,3-diaminopropionic acid is reported. The synthesis starts from commercially available N(α)-Boc-Asp(OBn)-OH and employs a Curtius rearrangement to establish the β-nitrogen. Proper protection of the α-nitrogen is essential for the success of the Curtius rearrangement.
- Englund, Ethan A.,Gopi, Hosahudya N.,Appella, Daniel H.
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p. 213 - 215
(2007/10/03)
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- Synthesis of aza and oxaglutamyl-p-nitroanilide derivatives and their kinetic studies with γ-glutamyltranspeptidase
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A new series of L-glutamic acid p-nitroanilide analogues has been synthesized and tested as substrates and inhibitors of rat kidney γ-glutamyltranspeptidase (GGT). Kinetic parameters (Km and kcat) were determined for each analogue and provide insight into the scope and limits of GGT catalytic efficiency.
- Lherbet, Christian,Morin, Mylene,Castonguay, Roselyne,Keillor, Jeffrey W.
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p. 997 - 1000
(2007/10/03)
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- 127. C-glycoside analogues of N4-(2-Acetamido-2-deoxy-β-D-glucopyranosyl)-L-asparagine: synthesis and conformational analysis of a cyclic C-glycopeptide
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The synthesis of C-glycosidic analogues 15-22 of N4-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-L-asparagine (ASn(N4GlcNAc)) possessing a reversed amide bond as an isosteric replacement of the N-glycosidic linkage is presented. The peptide cyclo(-D-Pro-Phe-Ala-CGaa-Phe-Phe-) (CGaa = C-glycosylated amino acid; 24) was prepared to demonstrate that 3-[(3-acetamido-2,6-anhydro-4,5,7-tri-O-benzyl-3-deoxy-β-D-glycero-D- guloheptonoyl)amino]-2-[(9H-fluoren-9-yloxycarbonyl)amino]propanoic acid (22) can be used in solid-phase peptide synthesis. The conformation of 24 was determined by NMR and molecular-dynamics (MD) techniques. Evidence is provided that the CGaa side chain interacts with the peptide backbone. The different C-glycosylated amino acids 15-21 were prepared by coupling 3-acetamido-2,6-anhydro-4,5,7-tri-O-benzyl-3-deoxy-β-D-glycero-D-gulo- heptonic acid (4) with diamino-acid derivatives 8-14 in 83-96% yield. The synthesis of 4 was performed from 2-(acetamido-3,4,6-tri-O-benzyl-2-deoxy-β-D-glucopyranosyl)tributylstannane (2) by treatment with BuLi and CO2 in 83% yield. Similarly, propyl isocyanat yielded the glycoheptonamide 7 in 52% from 2. Compound 2 was obtained from 2-acetamido-3,4,6-tri-O-benzyl-2-deoxy-D-glucopyranose (1) by chlorination and addition of tributyltinlithium in 74% yield. A procedure for a multigram-scale synthesis of 1 is given.
- Hoffmann, Matthias,Burkhart, Fred,Hessler, Gerhard,Kessler, Horst
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p. 1519 - 1532
(2007/10/03)
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- A selective protection of 2,3-diaminopropionic acid
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A two step selective protection of 2,3-diaminopropionic acid yields the useful diaminopropionic acid methyl ester 3a. Further manipulation yields 2(S)-(N-benzyloxycarbonylamino)-3-aminopropionic acid methyl ester hydrochloride 5 in >99.9%ee.
- Egbertson,Homnick,Hartman
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p. 703 - 709
(2007/10/02)
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- Synthesis and biological activity of (S)-2-amino-3-(2,5-dihydro-5-oxo-4-isoxazolyl)propanoic acid (TAN-950 A) derivatives
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(S)-2-Amino-3-(2,5-dihydro-5-oxo-4-isoxazolyl)propanoic acid (TAN-950 A (1)) is a novel amino acid antibiotic which shows a high affinity for glutamate receptors of the central nervous system. To improve the affinity for glutamate receptors, the structure
- Tamura,Matsushita,Iwama,Harada,Kishimoto,Itoh
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p. 1199 - 1212
(2007/10/02)
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