3190-70-3Relevant articles and documents
Cooperative hierarchical self-assembly of peptide dendrimers and linear polypeptides into nanoarchitectures mimicking viral capsids
Xu, Xianghui,Yuan, Hui,Chang, Jing,He, Bin,Gu, Zhongwei
, p. 3130 - 3133 (2012)
Peptidesomes are nanoparticles that are built by a two-step self-assembly of globular peptide dendrimers with lysine endgroups (red spheres in picture) and poly(L-leucine) carrying one glutamic acid residue (blue lines with red dot). These viral-capsid-mimicking nanoarchitectures exhibit high gene transfection efficacy and thus are promising nonviral vectors for biomedical applications. Copyright
Novel conditions for the Juliá-Colonna epoxidation reaction providing efficient access to chiral, nonracemic epoxides
Geller, Thomas,Gerlach, Arne,Krüger, Christa M.,Militzer, H.-Christian
, p. 5065 - 5067 (2004)
The addition of a phase-transfer catalyst significantly accelerates the Juliá-Colonna epoxidation reaction yielding chiral, nonracemic epoxy ketones. Furthermore, a reliable procedure for the preparation of highly active poly-L-leucine catalyst is reported.
A scalable synthesis of L-leucine-N-carboxyanhydride
Smeets,Van Der Weide,Meuldijk,Vekemans,Hulshof
, p. 757 - 763 (2005)
Due to its relevance in the synthesis of well-defined oligopeptides, the L-leucine-N-carboxyanhydride (leucine-NCA) synthesis was selected for fine chemical scale-up with a scope on application on larger scales. The heterogeneous gas-solid-liquid nature of the leucine-NCA synthesis implied a mass transfer limited reaction rate towards phosgenation and was investigated on bench scale. Upon scale increase, the liquid-gas mass transport of HCl is drastically reduced, retarding the reaction and consequently rendering the process unsuitable for scale-up. Addition of an HCl scavenger such as (+)-limonene prevented side reactions thus allowing a cost reduction, a considerably faster reaction, and minimization of the amount of phosgene source used. The modified leucine-NCA synthesis has successfully been made scalable, maintaining high product purity on a 1.0 dm3 scale.
PEG-polyaminoacid based micelles for controlled release of doxorubicin: Rational design, safety and efficacy study
Brunato, Silvia,Mastrotto, Francesca,Bellato, Federica,Bastiancich, Chiara,Travanut, Alessandra,Garofalo, Mariangela,Mantovani, Giuseppe,Alexander, Cameron,Preat, Veronique,Salmaso, Stefano,Caliceti, Paolo
, p. 21 - 37 (2021/05/19)
A library of amphiphilic monomethoxypolyethylene glycol (mPEG) terminating polyaminoacid co-polymers able to self-assemble into colloidal systems was screened for the delivery and controlled release of doxorubicin (Doxo). mPEG-Glu/Leu random co-polymers were generated by Ring Opening Polymerization from 5 kDa mPEG-NH2 macroinitiator using 16:0:1, 8:8:1, 6:10:1, 4:12:1 γ-benzyl glutamic acid carboxy anhydride monomer/leucine N-carboxy anhydride monomer/PEG molar ratios. Glutamic acid was selected for chemical conjugation of Doxo, while leucine units were introduced in the composition of the polyaminoacid block as spacer between adjacent glutamic repeating units to minimize the steric hindrance that could impede the Doxo conjugation and to promote the polymer self-assembly by virtue of the aminoacid hydrophobicity. The benzyl ester protecting the γ-carboxyl group of glutamic acid was quantitatively displaced with hydrazine to yield mPEG5kDa-b-(hydGlum-r-Leun). Doxo was conjugated to the diblock co-polymers through pH-sensitive hydrazone bond. The Doxo derivatized co-polymers obtained with a 16:0:1, 8:8:1, 6:10:1 Glu/Leu/PEG ratios self-assembled into 30–40 nm spherical nanoparticles with neutral zeta-potential and CMC in the range of 4-7 μM. At pH 5.5, mimicking endosome environment, the carriers containing leucine showed a faster Doxo release than at pH 7.4, mimicking the blood conditions. Doxo-loaded colloidal formulations showed a dose dependent cytotoxicity on two cancer cell lines, CT26 murine colorectal carcinoma and 4T1 murine mammary carcinoma with IC50 slightly higher than those of free Doxo. The carrier assembled with the polymer containing 6:10:1 hydGlu/Leu/PEG molar ratio {mPEG5kDa-b-[(Doxo-hydGlu)6-r-Leu10]} was selected for subsequent in vitro and in vivo investigations. Confocal imaging on CT26 cell line showed that intracellular fate of the carrier involves a lysosomal trafficking pathway. The intratumor or intravenous injection to CT26 and 4T1 subcutaneous tumor bearing mice yielded higher antitumor activity compared to free Doxo. Furthermore, mPEG5kDa-b-[(Doxo-hydGlu)6-r-Leu10] displayed a better safety profile when compared to commercially available Caelyx.
Synthesis of α-Amino Acid N-Carboxyanhydrides
Laconde, Guillaume,Amblard, Muriel,Martinez, Jean
supporting information, p. 6412 - 6416 (2021/08/30)
A simple phosgene- and halogen-free method for synthesizing α-amino acid N-carboxyanhydrides (NCAs) is described. The reaction between Boc-protected α-amino acids and T3P reagent gave the corresponding NCA derivatives in good yield and purity with no detectable epimerization. The process is safe, is easy-to-operate, and does not require any specific installation. It generates nontoxic, easy to remove byproducts. It can apply to the preparation of NCAs for the on-demand on-site production of either little or large quantities.
Polyamino acid carrier with acid-sensitive connecting arm in middle as well as preparation method and application of polyamino acid carrier
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Paragraph 0050-0053; 0054-0055, (2020/09/20)
The invention discloses a polyamino acid carrier with an acid-sensitive connecting arm in the middle as well as a preparation method and application of the polyamino acid carrier. The polyamino acid carrier contains a hydrophilic part, a hydrophobic part and a responsive connecting arm; a specific disulfide bond is introduced into the carrier design, the disulfide bond can be controllably broken into sulfydryl in vitro, the small molecule with the sulfydryl fragment or the gene with sulfydryl inherent on the surface is bonded with the protein drug again, and a covalent disulfide bond is formedto complete chemical bonding delivery of the drug. The polyamino acid carrier and the drug are bonded in a covalent bond manner, so that the drug can be stably transported in systemic circulation. When the carrier reaches high-metabolism and high-reducibility parts such as tumors or inflammations, disulfide bonds are broken again under the condition of high glutathione (GSH), and the activity ofthe drug is released and recovered. Therefore, the purposes of firstly masking the drug activity, then stably delivering the drug in vivo and recovering accurate regulation and control of the drug activity after the drug reaches a target position are achieved.
METHOD FOR PRODUCING AMINO ACID-N-CARBOXYLIC ACID ANHYDRIDE
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Paragraph 0067-0068; 0078, (2020/08/07)
PROBLEM TO BE SOLVED: To provide: a method for safely and efficiently producing amino acid-N-carboxylic acid anhydride; and a method for producing peptide by using the obtained amino acid-N-carboxylic acid anhydride. SOLUTION: The method for producing an amino acid-N-carboxylic acid anhydride according to the present invention is characterized in that the amino acid-N-carboxylic acid anhydride is represented by the following formula (II), and a step of irradiating a composition containing a halogenated methane and an amino acid compound represented by the following formula (I) with high energy light in the presence of oxygen is included. [In the formula, R1 represents an amino acid side chain group in which the reactive group is protected, and R2 represents H or the like.]. SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT
METHOD OF SYNTHESIZING N-CARBOXYANHYDRIDE USING FLOW REACTOR
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Paragraph 0092-0096; 0123-0124, (2020/03/26)
PROBLEM TO BE SOLVED: To provide a synthesis method that allows high-yield continuous production of a compound of interest in synthesis and production of N-carboxyanhydride (NCA) and the like using a flow reactor. SOLUTION: In a synthesis method using a flow reactor 100, a basic solution adjusted in advance to a pH of 7-14 becomes acidic with a pH of 0-7, or an acidic solution adjusted in advance to a pH of 0-7 becomes basic with a pH of 7-14, within 60 seconds after the start of mixture of at least two ingredient solutions. SELECTED DRAWING: Figure 1 COPYRIGHT: (C)2020,JPOandINPIT
Rapid and Mild Synthesis of Amino Acid N-Carboxy Anhydrides: Basic-to-Acidic Flash Switching in a Microflow Reactor
Otake, Yuma,Nakamura, Hiroyuki,Fuse, Shinichiro
supporting information, p. 11389 - 11393 (2018/08/28)
Polymerization of N-carboxy anhydrides (NCAs) is the primary process used to prepare polypeptides. The synthesis of various pure NCAs is key to the efficient synthesis of polypeptides. The only practical method that can be used to synthesize NCAs requires harsh acidic conditions that make acid-labile substrates unusable and results in an undesired ring opening of NCAs. Basic-to-acidic flash switching and subsequent flash dilution technology in a microflow reactor was used to demonstrate the synthesis of NCAs. It is both rapid (0.1 s) and mild (20 °C) and includes substrates containing acid-labile functional groups. The basic-to-acidic flash switching enabled both an acceleration of the desired NCA formation and avoided the undesired ring opening of NCAs. The flash dilution precluded the undesired decomposition of acid-labile functional groups. The developed process allowed the synthesis of various NCAs which cannot be readily synthesized using conventional batch methods.
Papain-catalysed mechanochemical synthesis of oligopeptides by milling and twin-screw extrusion: Application in the Juliá-Colonna enantioselective epoxidation
Ardila-Fierro, Karen J.,Crawford, Deborah E.,K?rner, Andrea,James, Stuart L.,Bolm, Carsten,Hernández, José G.
supporting information, p. 1262 - 1269 (2018/03/26)
The oligomerisation of l-amino acids by papain was studied in a mixer ball mill and in a planetary ball mill. The biocatalyst proved stable under the ball milling conditions providing the corresponding oligopeptides in good to excellent yields and with a variable degree of polymerisation. Both parameters were found to be dependent on the reaction conditions and on the nature of the amino acid (specifically on its side-chain size and hydrophobicity). In addition, the chemoenzymatic oligomerisation was demonstrated by utilising twin-screw extrusion technology, which allowed for a scalable continuous process. Finally, the synthesised oligo(l-Leu) 2b proved to be active as a catalyst in the Juliá-Colonna enantioselective epoxidation of chalcone derivatives.
