Evaluation of derivatives of 3-(2-oxo-1-pyrrolidine) hexahydro-1H-azepine-2-one as dermal penetration enhancers: side chain length variation and molecular modeling

The action of trypsin on the following amino acid derivatives has been investigated: the ethyl esters of ε-N-mono-, ε-N-di-, and ε-N-tri-methyl-L-lysine; the ethyl esters of the homologues of lysine and arginine; the methyl ester and amide of the α-N-benzoyl-DL-homolysine; the methyl esters and amides of the α-N-benzoyl derivatives of ε-N-di- and ε-N-tri-methyllysine; and poly ε-N-methyllysine. Derivatives of L-ornithine, DL-2,8-diaminooctanoic acid, ε-N-dimethyl-, ε-N-trimethyl-, and ε-N-formyl-L-lysine were not substrates of trypsin. ε-N-Dimethyl-L-lysine derivatives did not inhibit the action of trypsin on a specific substrate. DL-Homolysine derivatives were hydrolyzed with kcat's one to two orders of magnitude lower than those of lysine derivatives, but their Km's were only 1.5–3 times higher. ε-N-Methyl-L-lysine derivatives were hydrolyzed at rates similar to those for DL-homolysine derivatives, and had Km's 25–115 times those of lysine derivatives. Plots of Km and kcat/Km versus side-chain length of the substrate for the ethyl esters of all the homologues of lysine and arginine indicated a correlation between these kinetic constants and side-chain length, and that the best substrate would have a side-chain length between those of lysine and arginine. Poly-ε-N-methyl-L-lysine was degraded to small peptides by trypsin.

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Thermoresponsive Poly(2-oxazoline) Molecular Brushes by Living Ionic Polymerization: Kinetic Investigations of Pendant Chain Grafting and Cloud Point Modulation by Backbone and Side Chain Length Variation

Macromolecular Chemistry and Physics ◽

10.1002/macp.201200015 ◽

2012 ◽

Vol 213 (9) ◽

pp. 973-981 ◽

Cited By ~ 47

Author(s):

Ning Zhang ◽

Robert Luxenhofer ◽

Rainer Jordan

Keyword(s):

Cloud Point ◽

Chain Length ◽

Side Chain ◽

Length Variation ◽

Side Chain Length ◽

Molecular Brushes ◽

Polymerization Kinetic ◽

Kinetic Investigations

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New 6-Bromotryptamine Derivatives from Marine Bacterium Pseudoalteromonas rubra QD1 - 2 and the Impact of Side Chain Length on Their Cytotoxicity

Planta Medica ◽

10.1055/s-0033-1348634 ◽

2013 ◽

Vol 79 (10) ◽

Author(s):

S He ◽

L Ding ◽

X Yan

Keyword(s):

Chain Length ◽

Marine Bacterium ◽

Side Chain ◽

Side Chain Length ◽

The Impact ◽

Pseudoalteromonas Rubra

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Effects of Amino Acid Side-Chain Length and Chemical Structure on Anionic Polyglutamic and Polyaspartic Acid Cellulose-Based Polyelectrolyte Brushes

Polymers ◽

10.3390/polym13111789 ◽

2021 ◽

Vol 13 (11) ◽

pp. 1789

Author(s):

Dmitry Tolmachev ◽

George Mamistvalov ◽

Natalia Lukasheva ◽

Sergey Larin ◽

Mikko Karttunen

Keyword(s):

Glutamic Acid ◽

Chain Length ◽

Chemical Structure ◽

Side Chain ◽

Side Chains ◽

Side Chain Length ◽

Polyelectrolyte Brushes ◽

Grafting Density ◽

The Difference ◽

Cellulose Surface

We used atomistic molecular dynamics (MD) simulations to study polyelectrolyte brushes based on anionic α,L-glutamic acid and α,L-aspartic acid grafted on cellulose in the presence of divalent CaCl2 salt at different concentrations. The motivation is to search for ways to control properties such as sorption capacity and the structural response of the brush to multivalent salts. For this detailed understanding of the role of side-chain length, the chemical structure and their interplay are required. It was found that in the case of glutamic acid oligomers, the longer side chains facilitate attractive interactions with the cellulose surface, which forces the grafted chains to lie down on the surface. The additional methylene group in the side chain enables side-chain rotation, enhancing this effect. On the other hand, the shorter and more restricted side chains of aspartic acid oligomers prevent attractive interactions to a large degree and push the grafted chains away from the surface. The difference in side-chain length also leads to differences in other properties of the brush in divalent salt solutions. At a low grafting density, the longer side chains of glutamic acid allow the adsorbed cations to be spatially distributed inside the brush resulting in a charge inversion. With an increase in grafting density, the difference in the total charge of the aspartic and glutamine brushes disappears, but new structural features appear. The longer sides allow for ion bridging between the grafted chains and the cellulose surface without a significant change in main-chain conformation. This leads to the brush structure being less sensitive to changes in salt concentration.

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