65864-22-4Relevant articles and documents
MU OPIOID RECEPTOR MODULATORS
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Paragraph 0421; 0422; 0423; 0424, (2018/07/31)
Described herein, inter alia, are compositions and methods for modulating mu opioid receptor activity.
MU OPIOID RECEPTOR MODULATORS
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Paragraph 0373-0374; 0375-0376, (2017/01/26)
Described herein, inter alia, are compositions and methods for modulating mu opioid receptor activity.
Chiral perylene diimides: Building blocks for ionic self-assembly
Echue, Geraldine,Lloyd-Jones, Guy C.,Faul, Charl F. J.
supporting information, p. 5118 - 5128 (2015/03/30)
A chiral perylene diimide building block has been prepared based on an amine derivative of the amino acid L-phenylalanine. Detailed studies were carried out into the self-assembly behaviour of the material in solution and the solid state using UV/Vis, circular dichroism (CD) and fluorescence spectroscopy. For the charged building block BTPPP, the molecular chirality of the side chains is translated into the chiral supramolecular structure in the form of right-handed helical aggregates in aqueous solution. Temperature-dependent UV/Vis studies of BTPPP in aqueous solution showed that the self-assembly behaviour of this dye can be well described by an isodesmic model in which aggregation occurs to generate short stacks in a reversible manner. Wide-angle X-ray diffraction studies (WXRD) revealed that this material self-organises into aggregates with π-π stacking distances typical for π-conjugated materials. TEM investigations revealed the formation of self-assembled structures of low order and with no expression of chirality evident. Differential scanning calorimetry (DSC) and polarised optical microscopy (POM) were used to investigate the mesophase properties. Optical textures representative of columnar liquid-crystalline phases were observed for solvent-annealed samples of BTPPP. The high solubility, tunable self-assembly and chiral ordering of these materials demonstrate their potential as new molecular building blocks for use in the construction of chiro-optical structures and devices.
Process for lowering the viscosity of highly concentrated protein solutions
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Paragraph 0370, (2014/03/21)
A process of lowering the viscosity of a solution includes preparing a solution comprising a compound of formula I, at a concentration in the final formulation of between 10 and 250 mM, and a protein having at least one antibody fragment whose concentration is between 50 and 350 mg/mL and whose pH is between 5 and 8. The compound lowers the viscosity of the solution, which is difficult to inject, by a value of at least 15% relative to the viscosity of a solution of at least one protein having at least one antibody fragment of the same concentration and of the same pH not containing the compound.
Enzymatic synthesis of chiral phenylalanine derivatives by a dynamic kinetic resolution of corresponding amide and nitrile substrates with a multi-enzyme system
Yasukawa, Kazuyuki,Asano, Yasuhisa
, p. 3327 - 3332 (2013/01/15)
Mutant α-amino-ε-caprolactam (ACL) racemase (L19V/L78T) from Achromobacter obae with improved substrate specificity toward phenylalaninamide was obtained by directed evolution. The mutant ACL racemase and thermostable mutant D-amino acid amidase (DaaA) from Ochrobactrum anthropi SV3 co-expressed in Escherichia coli (pACLmut/pDBFB40) were utilized for synthesis of (R)-phenylalanine and non-natural (R)-phenylalanine derivatives (4-OH, 4-F, 3-F, and 2-F-Phe) by dynamic kinetic resolution (DKR). Recombinant E. coli with DaaA and mutant ACL racemase genes catalyzed the synthesis of (R)-phenylalanine with 84% yield and 99% ee from (RS)-phenylalaninamide (400 mM) in 22 h. (R)-Tyrosine and 4-fluoro-(R)-phenylalanine were also efficiently synthesized from the corresponding amide compounds. We also co-expresed two genes encoding mutant ACL racemase and L-amino acid amidase from Brevundimonas diminuta in E. coli and performed the efficient production of various (S)-phenylalanine derivatives. Moreover, 2-aminophenylpropionitrile was converted to (R)-phenylalanine by DKR using a combination of the non-stereoselective nitrile hydratase from recombinamt E. coli and mutant ACL racemase and DaaA from E. coli encoding mutant ACL racemase and DaaA genes. Copyright
Regioselective hydration and deprotection of chiral, dissymmetric iminodinitriles in the scope of an asymmetric strecker strategy
Rossi, Jean-Christophe,Marull, Marc,Boiteau, Laurent,Taillades, Jacques
, p. 662 - 668 (2007/10/03)
The controlled, selective decomposition of dissymmetric iminodinitriles (DIDN) of formula RCH(CN)-NH-C(CN)R′R″ (considered as N-protected alpha-aminonitriles), is a critical issue for an original asymmetric Strecker strategy previously outlined by us for the enantioselective synthesis of amino acids. This strategy, derived from Harada's work, involves a double sequence of (i) stereoselective Strecker condensation of a chiral ketone R′R″CO with NH3 and HCN, followed by (ii) stereoselective Strecker condensation with an aldehyde RCHO and HCN, then (iii) regioselective retro-Strecker decomposition of the DIDN intermediate to release the target alpha-aminonitrile. In addition to the use of quite simple, cheap cyclic ketones (e.g. carvone derivatives) as chiral auxiliaries, another great advantage of this strategy is that step (iii) enables the recovery of the chiral ketone and hence its reuse. While our previous investigations on step (iii) under various conditions, either preceded or followed by the hydration of the secondary nitrile group RH(CN)- into an amide, had shown insufficient selectivity, we succeeded in the regioselective hydration of the secondary nitrile of DIDN without significant racemisation, by using a large excess of hydrogen peroxide in methanolic/aqueous ammonia (pH 12.5) at low temperature. The resulting imino nitrile/amide compound was then classically decomposed in acidic medium through a retro-Strecker reaction, affording the chiral alpha-amino amide. Alternately, the regioselective retro-Strecker decomposition of the tertiary moiety of the DIDN was achieved by reaction with silver cation in aqueous nitric acid, also without significant racemisation, thus establishing an original, enantioselective synthesis of alpha-aminonitriles. In both reactions, the chiral ketonic auxiliary resulting from DIDN decomposition was recovered in good yields. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
Structural studies of [2′,6′-dimethyl-L-tyrosine1]endomorphin-2 analogues: Enhanced activity and cis orientation of the Dmt-Pro amide bond
Okada, Yoshio,Fujita, Yoshio,Motoyama, Takashi,Tsuda, Yuko,Yokoi, Toshio,Li, Tingyou,Sasaki, Yusuke,Ambo, Akihiro,Jinsmaa, Yunden,Bryant, Sharon D.,Lazarus, Lawrence H.
, p. 1983 - 1994 (2007/10/03)
Analogues of endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH2) (1) were designed to examine the importance of each residue on μ-opioid receptor interaction. Replacement of Tyr1 by 2′,6′-dimethyl-L-tyrosine (Dmt) (9-12) exerted profound effects: [Dmt1]EM-2 (9) elevated μ-opioid affinity 4.6-fold (Kiμ=0.15 nM) yet selectivity fell 330-fold as δ-affinity rose (Kiδ=28.2 nM). This simultaneous increased μ- and δ-receptor bioactivities resulted in dual agonism (IC50=0.07 and 1.87 nM, respectively). While substitution of Phe4 by a phenethyl group (4) decreased μ affinity (Kiμ=13.3 nM), the same derivative containing Dmt (12) was comparable to EM-2 but also acquired weak δ antagonism (pA2=7.05). 1H NMR spectroscopy revealed a trans configuration (1:2 to 1:3, cis/trans) in the Tyr-Pro amide bond, but a cis configuration (5:3 to 13:7, cis/trans) with Dmt-Pro analogues.
Synthesis of α-amino dithioesters and endothiodipeptides
Hartke, Klaus,Barrmeyer, Stephan
, p. 251 - 256 (2007/10/03)
The α-amino ester hydrochlorides (1) are converted into N-protected α-amino amides (3), α-amino thioamides (4) and α-amino dithiomethylesters (5). Condensation of 5 with the alkali salts of α-amino acids gives rise to the endothiodipeptide alkali salts (7). Johann Ambrosius Barth 1996.
Dithio and Thiono Esters, 55. - Synthesis of N-Protected, Optically Active α-Amino Thiono Esters
Brutsche, Andreas,Hartke, Klaus
, p. 921 - 926 (2007/10/02)
The N-protected α-amino amides 1 are O-alkylated with trialkyloxonium tetrafluoroborates to form the iminium salts 2.Sulfhydrolysis of 2 yields the α-amino thiono esters 3.This reaction sequence allows the preparation of enantiomerically pure 3.Key Words:
ENZYMIC SYNTHESIS OF OLIGOPETIDE - VI. THE MECHANISTIC FEATURES OF PEPSIN-CATALYSED PEPTIDE SYNTHESIS
Tseng, Min-Jen,Wu, Shih-Hsiung,Wang, Kung-Tsung
, p. 61 - 66 (2007/10/02)
The dipeptide Z-Phe-Phe-OBzl and tripeptide Z-Phe-Phe-Phe-OBzl were synthesized by pepsin catalysis from the incubation of Z-Phe and Phe-OBzl in the reaction solution.The yield ratio of two peptides in relation to reaction time was investigated by HPLC.Another example: The tripeptide Z-Phe-Leu-Phe-OBzl and tetrapeptide Z-Phe-Leu-Phe-Phe-OBzl were also synthesized concurrently from Z-Phe-Leu and Phe-OBzl by pepsin catalysis.These results may have important implication for the transpeptidation of pepsin.But, according to the report of Pellegrini and Luisi, the dipeptide, Z-Ph-Phe-OBzl, synthesized by pepsin catalysis was not contaminated with the tripeptide,Z-Phe-Phe-Phe-OBzl, and the yield was high.In order to investigate the discrepancies between our observation and those reported by Pellegrini and Luisi, a mechanism by which pepsin synthesizes the dipeptide, Z-Phe-Phe-OBzl, and tripeptide, Z-Phe-Phe-Phe-OBzl, is proposed and supporting data demonstrated by HPLC analysis.
