Colloidal and antibacterial properties of novel triple-headed, double-tailed amphiphiles: exploring structure-activity relationships and synergistic mixtures.

Two novel series of tris-cationic, tripled-headed, double-tailed amphiphiles were synthesized and the effects of tail length and head group composition on the critical aggregation concentration (CAC), thermodynamic parameters, and minimum inhibitory concentration (MIC) against six bacterial strains were investigated. Synergistic antibacterial combinations of these amphiphiles were also identified. Amphiphiles in this study are composed of a benzene core with three benzylic ammonium bromide groups, two of which have alkyl chains, each 8-16 carbons in length. The third head group is a trimethylammonium or pyridinium. Log of critical aggregation concentration (log[CAC]) and heat of aggregation (ΔHagg) were both inversely proportional to the length of the linear hydrocarbon chains. Antibacterial activity increases with tail length until an optimal tail length of 12 carbons per chain, above which, activity decreased. The derivatives with two 12 carbon chains had the best antibacterial activity, killing all tested strains at concentrations of 1-2µM for Gram-positive and 4-16µM for Gram-negative bacteria. The identity of the third head group (trimethylammonium or pyridinium) had minimal effect on colloidal and antibacterial activity. The antibacterial activity of several binary combinations of amphiphiles from this study was higher than activity of individual amphiphiles, indicating that these combinations are synergistic. These amphiphiles show promise as novel antibacterial agents that could be used in a variety of applications.

ß-amylase-like proteins function as transcription factors in Arabidopsis, controlling shoot growth and development.

Plants contain ß-amylase-like proteins (BAMs; enzymes usually associated with starch breakdown) present in the nucleus rather than targeted to the chloroplast. They possess BRASSINAZOLE RESISTANT1 (BZR1)-type DNA binding domains--also found in transcription factors mediating brassinosteroid (BR) responses. The two Arabidopsis thaliana BZR1-BAM proteins (BAM7 and BAM8) bind a cis-regulatory element that both contains a G box and resembles a BR-responsive element. In protoplast transactivation assays, these BZR1-BAMs activate gene expression. Structural modeling suggests that the BAM domain's glucan binding cleft is intact, but the recombinant proteins are at least 1000 times less active than chloroplastic ß-amylases. Deregulation of BZR1-BAMs (the bam7bam8 double mutant and BAM8-overexpressing plants) causes altered leaf growth and development. Of the genes upregulated in plants overexpressing BAM8 and downregulated in bam7bam8 plants, many carry the cis-regulatory element in their promoters. Many genes that respond to BRs are inversely regulated by BZR1-BAMs. We propose a role for BZR1-BAMs in controlling plant growth and development through crosstalk with BR signaling. Furthermore, we speculate that BZR1-BAMs may transmit metabolic signals by binding a ligand in their BAM domain, although diurnal changes in the concentration of maltose, a candidate ligand produced by chloroplastic ß-amylases, do not influence their transcription factor function.

Hydra amphiphiles: Using three heads and one tail to influence aggregate formation and to kill pathogenic bacteria.

Hydra amphiphiles mimic the morphology of the mythical multi-headed creatures for which they are named. Likewise, when faced with a pathogenic bacterium, some hydra derivatives are as destructive as their fabled counterparts were to their adversaries. This report focuses on eight new tricephalic (triple-headed), single-tailed amphiphiles. Each amphiphile has a mesitylene (1,3,5-trimethylbenzene) core, two benzylic trimethylammonium groups and one dimethylalkylammonium group with a linear hydrophobe ranging from short (C8H17) to ultralong (C22H45). The logarithm of the critical aggregation concentration, log(CAC), decreases linearly with increasing tail length, but with a smaller dependence than that of ionic amphiphiles with fewer head groups. Tail length also affects antibacterial activity; amphiphiles with a linear 18 or 20 carbon atom hydrophobic chain are more effective at killing bacteria than those with shorter or longer chains. Comparison to a recently reported amphiphilic series with three heads and two tails allows for the development of an understanding of the relationship between number of tails and both colloidal and antibacterial properties.