Number Of Primary Amines Research Articles

Available method for the synthesis of <i>E</i>-<i>N</i>-substituted-2-diphenylphosphorylaziridines

An available method for the synthesis of 2-diphenylphosphoryl- N -substituted aziridines with high yields has been developed by the interaction of (1,2-dibromoethyl)(diphenyl)phosphine oxide with a number of primary amines, in particular, methyl-, ethyl-, isopropyl-, tert -butyl-, cyclohexyl- and benzylamines at room temperature in the presence of sodium hydroxide. The antibacterial activity of obtained compounds was studied.

Brevinin-2R-linked polyethylenimine as a promising hybrid nano-gene-delivery vector.

Objective(s):Polyethylenimine (PEI) is one of the most widely used polymers in gene delivery. The aim of this study was to modify PEI by replacing some of its primary amines with Brevinin 2R (BR-2R) peptide in order to increase the efficiency of gene delivery.Materials and Methods:Polyethylenimine was modified by BR-2R peptide by two different approaches; A) conjugation methods including (І) using succinimidyl 3-(2-pyridyldithio) propionate (SPDP), (П) EDC/NHS protocol and (ПІ) EDC/NHS+6-bromohexanoic acid protocol, and B) physical interaction method. The modified polymers were characterized for their ability of plasmid condensation, number of primary amines, size and zeta potential. The transfection efficiency and cytotoxicity were evaluated on HEK293, L929, WEHI164 and Neuro2A cell lines by green fluorescent protein (GFP)-based plasmid (pGFP) reporter gene and viability assays, respectively. Apoptosis induction ability was also evaluated via PI/Annexin V assay. Results:Polyplex had size and zeta potential between 200-270 nm and +21.5- +28.4 mV, respectively. All vectors were able to condense plasmid DNA in C/P=4 (carrier-plasmid ratio). Transfection results on the Neuro2A cell line showed that the vector containing the BR-2R peptide, which was synthesized using EDC-NHS protocol had the best transfection efficiency. Conclusion:Our results showed that conjugation of Brevinin 2R as cell penetrating peptide to polyethyleneimine could enhance the transfection ability of the polymer.

BR2 cell penetrating peptide improved the transfection efficiency of modified polyethyleneimine

Polyethyleneimine (PEI) is one of the most widely used polymers in gene delivery. Cell penetrating peptides (CPPs) are a group of peptides that can transfer materials from the membrane to the cytoplasm and nucleus. The aim of this study was to modify PEI with three different CPPs as a cationic polymer in order to investigate and compare their efficiency in gene delivery. The CPP-modified polymers were evaluated in terms of plasmid condensation, buffering capacity and number of primary amines. The prepared nanoparticles were examined for size, zeta potential, transfection efficiency and cytotoxicity in LNCAP cells. The resulting nanoparticles had a particle size between 183 and 313 nm. Measuring the zeta potential of the vectors indicated that the charge of the nanoparticles is between 21 and 25 mV. Vectors can condense plasmid in carrier-plasmid ratio of 4. Transfection results on the LNCAP cell line showed that the vector containing the BR2 peptide had the best transfection activity. In the cytotoxicity test, it was observed that vector containing CyLoP1 in carrier-plasmid ratio of 4 had the highest cell cytotoxicity. In conclusion, conjugation of CPPs to PEI due to physicochemical changes of the polymer resulted in improved transfection activity.

Stoichiometries and Energetics of Cationic Nanoparticle-Membrane Complexes

The nanoparticle-membrane interaction is essential to nanotheraputic design and nanotoxicity concerns. The equilibrium structure was determined for phospholipid membranes interacting with one type of nanoparticle, poly(amidoamine) dendrimers, at the atomistic and molecular scale via both experimental and theoretical approaches. The resulting dendrimer-phospholipid complex depends on both the number of primary amines per dendrimer and the dendrimer size. Large dendrimers (> 7 nm diameter) induce vesicle-encased dendrimers and significant membrane disruption. In contrast, small dendrimers (< 5 nm diameter) bind to the membrane surface without individually inducing significant membrane disruption. Techniques such as isothermal titration calorimetry (ITC), molecular dynamics (MD), and differential scanning calorimetry (DSC) were used for examination of the equilibrium structures and identifying the mechanisms of nanoparticle-induced membrane disruption.Third-, fifth-, and seventh-generation poly(amidoamine) dendrimers (G3, G5, and G7, respectively) are shown here in complexes with phospholipids. The stoichiometries and dimensions of the dendrimer-lipid complexes indicate small dendrimers (G3) saturate with lipids on a planar membrane, medium-sized dendrimers (G5) induces local membrane curvature and/or binds to multiple bilayer surfaces, and each larger dendrimer (G7) becomes encased by a lipid vesicle. These understandings will guide nanoparticle design in both medical and industrial applications.View Large Image | View Hi-Res Image | Download PowerPoint Slide

Ni(II) and Ni(I) forms of pentaalkylamide derivatives of cofactor F 430 of Methanobacterium thermoautotrophicum

A series of pentaalkylamide forms of F 430 and of its 12,13-diepimer have been generated and characterized. Carbodiimide-assisted N-hydroxysulfosuccinimide activation of all five peripheral carboxylates of the F 430 macroacyle allows nucleophilid attack by a number of primary amines (RNH 2R- =CH 3-,CH 3CH 2-,CF 3CH 3 (CH 2) 3-) generating the pentaalkylamide derivatives. The identity of each derivative has been verified by fast-atom bombardment mass spectrometry (FAB-MS). The solubility of these derivatives in aprotic organic solvents varies as the amine alkyl substituent (R-) is changed. Electrochemical measurements have shown that the Ni(II/I) reduction potentials in N,N-dimethylformamide (DMF) are ∼−1 V (Ag/AgCl). Reduction by sodium amalgam in THF generates the Ni(I) form of the F 430 diepimer pentabutylamide. The visible and EPR spectra of this Ni(I) species are very similar to the corresponding spectra of Ni(I) F 430M (Jaun, B. and Pfaltz, A. (1986) J. Chem. Soc. Chem. Commun. 1327–1329).

New mitomycin analogs produced by directed biosynthesis.

When the normal fermentation medium for the production of mitomycin C with Streptomyces caespitosus is supplemented with a number of primary amines, two new types of mitomycin analogs described as Type I and Type II are produced. Type I analogs are related to mitomycin C with the amine substitution at position C7 on the mitosane ring. Type II analogs also contain the same substitutions at C7 but the conformation of the mitosane ring is related to mitomycin B having an OH at positions C9a and a methyl substituted aziridine. The products obtained from the supplementation of the medium with methylamine, ethylamine, propylamine, propargylamine and 2-methylallylamine were isolated and characterized. In all cases the Type I analogs are more active in a prophage induction test and against L1210 lymphatic leukemia in mice. A number of other amines have been tested and shown to yield new products that have not yet been isolated. No secondary amines are incorporated.

5-Hydroxy-N-methylpyroglutamate Synthetase: PURIFICATION AND MECHANISM OF ACTION

Abstract The enzyme catalyzing the formation of 5-hydroxy-N-methylpyroglutamate has been purified. This enzyme is inactivated by a number of sulfhydryl reagents; however, this inactivation can be prevented by 0.10 m α-ketoglutarate, but not by 0.20 m methylamine. The enzymatic reaction is specific for α-ketoglutarate but a number of primary amines can replace methylamine as substrates for the enzyme. The enzyme-catalyzed hydrolysis of 5-hydroxy-N-methylpyroglutamate is proportional to enzyme over a very narrow range of protein concentration, and the amount of enzyme required to saturate the system is dependent on the substrate concentration. These results are consistent with the hypothesis that N-methyl-α-ketoglutaramate, rather than 5-hydroxy-N-methylpyroglutamate, is the true product of the enzymatic reaction. Measurements of 5-hydroxy-N-methylpyroglutamate formation in the presence of n-propylamine or ethylamine result in alternate substrate inhibition patterns which are consistent with an ordered sequential kinetic mechanism. The enzyme-catalyzed hydrolyses of N-methyl-α-ketoglutaramate and a substrate analogue, α-ketoglutaramate, are noncompetitively inhibited by methylamine when α-keto-glutarate release is used to measure these reactions. However, no inhibition is observed if ammonia release is used as an assay. The decrease in α-ketoglutarate release can be quantitatively accounted for by the formation of 5-hydroxy-N-methylpyroglutamate. These results are consistent with the rate-limiting formation of an α-ketoglutaryl enzyme intermediate.