- Designed proteinoid polymers and nanoparticles encapsulating risperidone for enhanced antipsychotic activity
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Background: Nanoparticles (NPs) incorporating drug formulations can be used to facilitate passage through biological barriers including the blood–brain barrier (BBB) and increase drug delivery and bioavailability. Hence, NP-based administration may enhance the efficiency of current antipsychotics. Encapsulation within NPs can resolve aqueous solubility problems that not only reduce permeability through the BBB but also affect targeting. The present study describes a new drug delivery system based on proteinoid NPs to explore the possibility of improving drug efficacy. Risperidone (RSP) is a commonly used atypical antipsychotic medication, and was therefore selected for encapsulation by proteinoid NPs. Results: Proteinoid polymers with high molecular weight and low polydispersity were synthesized from l-amino acids and poly-l-lactic acid (PLLA) by thermal step-growth polymerization mechanism. RSP-loaded proteinoid NPs were then prepared using a self-assembly process in the presence of RSP, followed by PEGylation. The optimal PEGylated RSP-loaded NPs were characterized in terms of diameter and size distribution, drug loading, ζ-potential, cytotoxicity, biodistribution, and psychopharmacological effects. The findings indicate significantly higher antipsychotic activity of drug-loaded proteinoid NPs compared to free RSP. Conclusions: Proteinoid NPs enhance RSP delivery and may potentially increase drug efficiency by reducing dosage and side effects.[Figure not available: see fulltext.].
- Einat, H.,Grinberg, I.,Lugasi, L.,Margel, S.,Okun, E.,Rudnick-Glick, S.
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- New chemosynthetic route to linear ε-poly-lysine
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ε-Poly-lysine (ε-PL) is an uncommon cationic, naturally-occurring homopolymer produced by the fermentation process. Due to its significant antimicrobial activity and nontoxicity to humans, ε-PL is now industrially produced as an additive, e.g. for food and cosmetics. However, the biosynthetic route can only make polymers with a molecular weight of about 3 kDa. Here, we report a new chemical strategy based on ring-opening polymerization (ROP) to obtain ε-PL from lysine. The 2,5-dimethylpyrrole protected α-amino-ε-caprolactam monomer was prepared through cyclization of lysine followed by protection. ROP of this monomer, followed by the removal of the protecting group, 2,5-dimethylpyrrole, ultimately yielded ε-PL with varying molecular weights. The structure of this chemosynthetic ε-PL has been fully characterized by 1H NMR, 13C NMR, and MALDI-TOF MS analyses. This chemosynthetic ε-PL exhibited a similar pKa value and low cytotoxicity as the biosynthetic analogue. Using this new chemical strategy involving ROP without the need for phosgene may enable a more cost effective production of ε-PL on a larger-scale, facilitating the design of more advanced biomaterials.
- Tao, Youhua,Chen, Xiaoyu,Jia, Fan,Wang, Shixue,Xiao, Chunsheng,Cui, Fengchao,Li, Yunqi,Bian, Zheng,Chen, Xuesi,Wang, Xianhong
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- Chiral discrimination controlled by the solvent dielectric constant
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Chiroselective molecular recognition accompanied by a change in configuration of a target substrate has been studied. (RS)-α-Amino-ε- caprolactam 1 was used as the target substrate to be resolved while N-tosyl-(S)-phenylalanine 2 was used as the chiral selector. The dielectric constant (ε) of the solvent was found to have a profound effect on the chiroselective molecular recognition. The specific chiral selector (S)-2 not only recognized both enantiomers (R)- and (S)-1 individually to be deposited as the less-soluble salt from the different solvent but also controlled the configuration and diastereomeric excess of the less-soluble diastereomeric salt by simple adjustment of the solvents dielectric constant. The chiroselective recognition mechanism was examined based on the crystal structures of the salts, (S)-1·(S)-2·H2O and (R)-1·(S)-2, obtained from the resolution process.
- Sakai, Kenichi,Sakurai, Rumiko,Hirayama, Noriaki
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- Design, synthesis and cytotoxicity of bengamide analogues and their epimers
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Starting from d-glycero-d-gulo-heptonic acid γ-lactone and amino acids, a number of diastereoisomeric bengamide analogues were synthesized. Optimization of the reaction conditions revealed that microwave irradiation assistance is a powerful method for the preparation of aminolactams, as well as for the coupling reactions of the lactone 5 with aminolactams. Cytotoxic activity evaluation against six cancer cell lines (KB, HepG2, LU1, MCF7, HL60, and Hela) demonstrated that the configuration of C-2′ seems to be critical for the cytotoxic activity of compounds 8b (2′R) and 8a (2′S). Additionally, comparison of cytotoxicity of the protected acetonide compounds with that of their corresponding deprotected bengamide analogues suggested that the flexibility of the ketide side chain should be required for their cytotoxic activity.
- Phi, Thi Dao,Doan Thi Mai, Huong,Tran, Van Hieu,Truong, Bich Ngan,Tran, Tuan Anh,Vu, Van Loi,Chau, Van Minh,Pham, Van Cuong
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- Design, synthesis and properties investigation of Nα-acylation lysine based derivatives
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Amino acid-based compounds have attracted attention as environmentally friendly bio-based materials. Our group has recently developed a novel family of Nα-acylation lysine based derivatives. We introduced long chain acyl groups at the Nα position selectively by a new synthetic route that avoided the process of amino protection and deprotection. Sodium Nα-octanamide lysine (C8), sodium Nα-capramide lysine (C10) and sodium Nα-lauramide lysine (C12) can self-assemble into vesicles spontaneously. As a result, not only do they have potential in drug delivery system but also they may be used as bio-based surfactants applied in cosmetics and other industries.
- Shi, Ting-Ting,Fang, Zheng,Zeng, Wen-Bo,Yang, Zhao,He, Wei,Guo, Kai
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Read Online
- Synthesis of bengamide E analogues and their cytotoxic activity
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A series of bengamide E analogues were prepared from the corresponding polyketide chain and amino acids via amide coupling reactions. Opening of the polyketide chain lactone ring with α-aminolactams was successfully achieved under microwave irradiation in the presence of sodium 2-ethyl hexanoate. A cytotoxic activity evaluation against a panel of cancer cell lines (KB, HepG-2, Lu-1, MCF-7, HL-60 and Hela) indicated that the 2′R analogues were generally more cytotoxic than the 2′S analogues. Additionally, several analogues exhibited selective inhibition against various cancer cell lines: compounds 32a and 32b selectively inhibited MCF-7 cells, while 33b and 35b were more sensitive toward Lu-1 and HepG-2, respectively. Notably, some of the synthetic analogues possess cytotoxic activities with IC50 values less than 1?μM.
- Phi, Thi Dao,Mai, Huong Doan Thi,Tran, Van Hieu,Vu, Van Loi,Truong, Bich Ngan,Tran, Tuan Anh,Chau, Van Minh,Pham, Van Cuong
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supporting information
p. 1830 - 1833
(2017/04/21)
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- PROTEINOID COMPOUNDS, PROCESS OF PREPARING SAME AND USES THEREOF
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Proteinoid compounds characterized by a molecular weight (Mw) of at least 15,000 Da, processes of preparing such compounds and methods of use thereof, are provided. A method of monitoring the presence and metastases of cancer in a body of an individual is further disclosed.
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Sheet 23 of 36
(2017/04/11)
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- The Role of a Nonribosomal Peptide Synthetase in l -Lysine Lactamization during Capuramycin Biosynthesis
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Capuramycins are one of several known classes of natural products that contain an l-Lys-derived l-α-amino-caprolactam (l-ACL) unit. The α-amino group of l-ACL in a capuramycin is linked to an unsaturated hexuronic acid component through an amide bond that was previously shown to originate by an ATP-independent enzymatic route. With the aid of a combined in vivo and in vitro approach, a predicted tridomain nonribosomal peptide synthetase CapU is functionally characterized here as the ATP-dependent amide-bond-forming catalyst responsible for the biosynthesis of the remaining amide bond present in l-ACL. The results are consistent with the adenylation domain of CapU as the essential catalytic component for l-Lys activation and thioesterification of the adjacent thiolation domain. However, in contrast to expectations, lactamization does not require any additional domains or proteins and is likely a nonenzymatic event. The results set the stage for examining whether a similar NRPS-mediated mechanism is employed in the biosynthesis of other l-ACL-containing natural products and, just as intriguingly, how spontaneous lactamization is avoided in the numerous NRPS-derived peptides that contain an unmodified l-Lys residue.
- Liu, Xiaodong,Jin, Yuanyuan,Cui, Zheng,Nonaka, Koichi,Baba, Satoshi,Funabashi, Masanori,Yang, Zhaoyong,Van Lanen, Steven G.
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p. 804 - 810
(2016/05/19)
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- The reductive cleavage of picolinic amides
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Treatment of picolinic amides with excess zinc in aqueous hydrochloric acid at room temperature affords the corresponding amines in good to excellent yields. The mild reaction conditions exhibit useful functional group tolerance and facilitate the application of the picolinic amide moiety as a protecting group which can be easily introduced and selectively removed.
- O'Donovan, Daniel H.,De Fusco, Claudia,Spring, David R.
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supporting information
p. 2962 - 2964
(2016/07/06)
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- Direct amidation of unprotected amino acids using B(OCH2CF3)3
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A commercially available borate ester, B(OCH2CF3)3, can be used to achieve protecting-group free direct amidation of α-amino acids with a range of amines in cyclopentyl methyl ether. The method can be applied to the synthesis of medicinally relevant compounds, and can be scaled up to obtain gram quantities of products.
- Lanigan, Rachel M.,Karaluka, Valerija,Sabatini, Marco T.,Starkov, Pavel,Badland, Matthew,Boulton, Lee,Sheppard, Tom D.
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supporting information
p. 8846 - 8849
(2016/07/22)
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- Α-production of ε-caprolactam aminosilicone-
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PROBLEM TO BE SOLVED: To provide a new method for efficiently producing α-amino-ε-caprolactam which is the target compound directly from lysine or a salt thereof. SOLUTION: By using a method for producing α-amino-ε-caprolactam, in which lysine or a salt thereof is heated in a mixed solution of an alcohol and water with a ratio of alcohol/water (volume ratio) of 1-99, and dehydrated and cyclized, the α-amino-ε-caprolactam is rapidly produced with a good yield. Preferably the alcohol is methanol. COPYRIGHT: (C)2012,JPOandINPIT
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Paragraph 0023-0035
(2018/08/02)
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- SEPARATING AGENT FOR CHROMATOGRAPHY
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A separating agent for chromatography is provided that is useful for the separation of specific compounds, e.g., for the optical resolution of amino acids. This separating agent for chromatography provides a higher productivity and contains a crown ether-like cyclic structure and optically active binaphthyl. This separating agent for chromatography containing a crown ether-like cyclic structure and optically active binaphthyl is provided by introducing a substitution group for binding to carrier into a specific commercially available 1,1′-binaphthyl derivative that has substituents at the 2, 2′, 3, and 3′ positions, then introducing a crown ether-like cyclic structure, and subsequently chemically bonding the binaphthyl derivative to the carrier through the substitution group for binding to carrier.
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Paragraph 0074; 0075
(2013/08/15)
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- METHOD FOR MAKING ALPHA-AMINO-EPSILON-CAPROLACTAM USING MIXED SUPER CRITICAL FLUIDS
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The present invention can involve a method of synthesizing α-amino-ε-caprolactam. The method can comprise heating a salt of L-lysine in a solvent comprising an alcohol under Super Critical Fluid conditions. The methods can comprise heating a salt of L-lysine in a solvent comprising an alcohol and deaminating the reaction product. In various embodiments, the invention can include methods of converting biomass into nylon 6, The methods can comprise heating L-lysine in a solvent comprising an alcohol to produce α-amino-ε-caprolactam, deaminating to produce ε-caprolactam and polymerizing into nylon 6, wherein the L-lysine is derived from biomass. In other embodiments, the present invention can include methods of making nylon 6. The methods can comprise synthesizing ε-caprolactam and then polymerizing, wherein the ε-caprolactam is derived from L-lysine.
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Page/Page column 4
(2012/04/10)
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- COMPOSITIONS AND METHODS FOR CYCLOFRUCTANS AS SEPARATION AGENTS
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The present invention relates to derivatized cyclofructan compounds, compositions comprising derivatized cyclofructan compounds, and methods of using compositions comprising derivatized cyclofructan compounds for chromatographic separations of chemical species, including enantiomers. Said compositions may comprise a solid support and/or polymers comprising derivatized cyclofructan compounds.
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Page/Page column 45-49; 60
(2010/12/31)
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- Amino-caprolactam derivatives as γ-secretase inhibitors
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A series of amino-caprolactam sulfonamides were developed from a screening hit. Compounds with good in vitro and in vivo γ-secretase activity are reported.
- Parker, Michael F.,Bronson, Joanne J.,Barten, Donna M.,Corsa, Jason A.,Du, Wengsheng,Felsenstein, Kevin M.,Guss, Valerie L.,Izzarelli, Darcy,Loo, Alice,McElhone, Kate E.,Marcin, Larry R.,Padmanabha, Ramesh,Pak, Roger,Polson, Craig T.,Toyn, Jeremy H.,Varma, Sam,Wang, Jian,Wong, Victoria,Zheng, Ming,Roberts, Susan B.
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p. 5790 - 5795
(2008/03/13)
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- Resolution of α-aminolactams by inclusion complexation with chiral host compounds
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3-Aminopiperidin-2-one and α-amino-ε-caprolactam were efficiently resolved by inclusion complexation with a chiral host compound, (R,R)-(-)-trans-4,5-bis(hydroxydiphenylmethyl)-1,4-dioxaspiro[4.5]decane . The amino substituent on the lactam ring was found to play an important role in efficient chiral recognition in the inclusion crystals.
- Urbanczyk-Lipkowska, Zofia,Fukuda, Noriaki,Tanaka, Koichi
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p. 1254 - 1256
(2008/02/12)
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- SYNTHESIS OF CAPROLACTAM FROM LYSINE
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In various embodiments, the present invention can involve a method of synthesizing α-amino-ε -caprolactam. The method can comprise heating a salt of L-lysine in a solvent comprising an alcohol. In other embodiments, the present invention can involve methods for synthesizing ε-caprolactam. The methods can comprise heating a salt of L-lysine in a solvent comprising an alcohol and deaminating the reaction product. In various embodiments, the invention can include methods of converting biomass into nylon 6. The methods can comprise heating L-lysine in a solvent comprising an alcohol to produce α-amino -ε- caprolactam, deaminating to produce ε-caprolactam and polymerizing into nylon 6, wherein the L-lysine is derived from the biomass. In other embodiments, the present invention can include methods of making nylon 6. The methods can comprise synthesizing ε-caprolactam and then polymerizing, wherein the ε--caprolactam is derived from L-lysine.
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Page/Page column 7; 9
(2008/06/13)
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- Preparation, characterization, DNA binding, and in Vitro cytotoxicity of the enantiomers of the platinum(II) complexes N-methyl-, N-ethyl- and N,N- dimethyl-(R)- and -(S)-3-aminohexahydroazepinedichloroplatinum(II)
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A series of chiral diaminedichloroplatinum(II) complexes derived from [Pt(ahaz)Cl2] (ahaz = 3-aminohexahydroazepine) have been synthesized and tested for cytotoxic activity. Novel synthetic pathways were developed to produce the structural derivatives of the ahaz ligand, with alkyl substituents on the exocyclic nitrogen atom. The platinum(II) complexes of these ligands were synthesized and characterized by NMR and CD spectroscopy, confirming isomeric and enantiomeric purity. The crystal structures of three of these complexes, [Pt(S-meahaz)Cl2], [Pt(R-etahaz)Cl2], and [Pt(S- dimeahaz)Cl2] (meahaz = N-methylahaz, etahaz = N-ethylahaz, dimeahaz = N,N- dimethylahaz), have been determined to establish the orientation of the protons and alkyl substituents on the nitrogen donor atoms. In vitro assays of the cytotoxic activity of the complexes have revealed a significant and reproducible enantioselective trend with the R-enantiomers more active than the S-enantiomers in all cell lines. Increasing the steric bulk on the amine groups was found to have only a modest effect on activity. No enantioselectivity was observed in the binding of R- and S-[Pt(etahaz)Cl2] to calf-thymus DNA.
- Rezler, Evonne M.,Fenton, Ronald R.,Esdale, Warren J.,McKeage, Mark J.,Russell, Pamela J.,Hambley, Trevor W.
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p. 3508 - 3515
(2007/10/03)
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- A Novel Synthetic Route to Enantiomers of ε-Hydroxynorleucine and ε-Chloronorleucine from L- and D,L-Lysine
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Thermal rearrangement of (S)- or (R)-hexahydro-1-nitroso-3-phthalimido-2H-azepin-2-one to te corresponding lactone followed by nucleophilic ring opening of the latter gives ε-chloro- or ε-hydroxynorleucine.
- Belyaev, Alexander A.
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p. 439 - 440
(2007/10/02)
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