Effects of side chain length of 10-methyl-aplog-1, a simplified analog of debromoaplysiatoxin, on PKC binding, anti-proliferative, and pro-inflammatory activities

Abstract 10-Methyl-aplog-1 (1), a simplified analog of debromoaplysiatoxin, exhibits a high binding affinity for protein kinase C (PKC) isozymes and potent antiproliferative activity against several cancer cells with few adverse effects. A recent study has suggested that its phenol group in the side chain is involved in hydrogen bonding and CH/π interactions with the binding cleft-forming loops in the PKCδ-C1B domain. To clarify the effects of the side chain length on these interactions, four analogs of 1 with various lengths of side chains (2-5) were prepared. The maximal PKC binding affinity and antiproliferative activity were observed in 1. Remarkably, the introduction of a bromine atom into the phenol group of 2 increased not only these activities but also proinflammatory activity. These results indicated that 1 has the optimal side chain length as an anticancer seed. This conclusion was supported by docking simulations of 1-5 to the PKCδ-C1B domain.

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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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