Synthesis of a membrane-insertable, sodium cation conducting channel: kinetic analysis by dynamic sodium-23 NMR

Nakano, Akio; Xie, Qingshan; Mallen, Jesus; Echegoyen, Luis; Gokel, George W.

doi:10.1021/ja00159a083

Cited by 148 publications

(67 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A number of different approaches have been tried over the years since the initial preparation of 1 [54]. The synthetic sequence in current favor in our lab is shown in the scheme below.…”

Section: Synthesis and Characterizationmentioning

confidence: 99%

Coordination and transport of alkali metal cations through phospholipid bilayer membranes by hydraphile channels

Gokel

Daschbach

2008

Coordination Chemistry Reviews

Self Cite

View full text Add to dashboard Cite

Hydraphiles are synthetic ionophores that were designed to mimic some properties of protein channels that conduct such cations as sodium. They use macrocyclic (crown) polyethers as amphiphilic headgroups and as entry and exit portals. Their overall length is controlled by covalent links between the two headgroups (distal macrocycles) and the "central relay" unit, typically also an azacrown. The hydraphiles insert in the bilayer membranes of synthetic phospholipid vesicles or vital cells and mediate the transport of cations. The hydraphiles were intended to be models but they are functional channels. Because they are symmetric, they are non-rectifying but they show open-close behavior characteristic of natural channels. Because they are non-rectifying, when they insert into a microbial membrane, they lead to a rapid change in osmotic balance that proves fatal to bacteria.

show abstract

“…A number of different approaches have been tried over the years since the initial preparation of 1 [54]. The synthetic sequence in current favor in our lab is shown in the scheme below.…”

Section: Synthesis and Characterizationmentioning

confidence: 99%

Coordination and transport of alkali metal cations through phospholipid bilayer membranes by hydraphile channels

Gokel

Daschbach

2008

Coordination Chemistry Reviews

Self Cite

View full text Add to dashboard Cite

show abstract

“…These sidearms were designed to serve as intra-membrane anchors to stabilize the channel in the bilayer. 16 The compounds reported here incorporate the features described above but integrate amide residues at various positions within the channel. The influence of these strategically placed amide residues on sodium cation transport has been assayed analytically and in vivo and the results are reported below.…”

Section: Introductionmentioning

confidence: 99%

The influence of varied amide bond positions on hydraphile ion channel activity

et al. 2006

Self Cite

View full text Add to dashboard Cite

Hydraphile compounds have been prepared in which certain of the amine nitrogens have been replaced by amide residues. The amide bonds are present either in the sidearm, the side chain, or the central relay. Sodium cation transport through phospholipid vesicles mediated by each hydraphile was assessed. All of the amide-containing hydraphiles showed increased levels of Na + transport compared to the parent compound, but the most dramatic rate increase was observed for sidearm amine to amide replacement. We attribute this enhancement to stabilization of the sidearm in the bilayer to achieve a better conformation for ion conduction. Biological studies of the amide hydraphiles with E. coli and B. subtilis showed significant toxicity only with the latter. Further, the consistency between the efficacies of ion transport and toxicity previously observed for non-amidic hydraphiles was not in evidence.

show abstract

“…34 The original hydraphile design envisioned the two distal macrocycles as both head groups and entry and exit portals for transient cations. 40 The fact that indole's H-bond interactions prevented transport strongly supported this expectation. A hypothesis that tryptophan might also provide head group function engendered the synthesis of a central macrocycle having chains terminated by this amino acid.…”

Section: Meisel Jw Et Al: Synthetic Antimicrobial J Explor Res Pharmmentioning

confidence: 88%

Tryptophan in Membrane-Active Synthetic Antimicrobials

2017

JERP

View full text Add to dashboard Cite

Herein, we summarize the background data that has led to a new class of antimicrobial amphiphiles and present recent results showing reversal of resistance to antibiotics in an Escherichia coli strain incorporating a tetracycline-selective efflux pump. In addition, two types of amphiphiles that show antibiotic potency enhancement or resistance reversal are discussed, along with our knowledge on the evolution that led to the active structures. One family is based on macrocyclic crown polyethers, which are known to insert into both liposomal and bacterial bilayers; these compounds are termed as hydraphiles and consist of three diazacrown rings linked by alkyl spacers and terminated by benzyl groups. In contrast, the second type of amphiphiles use tryptophans as the terminal, membrane anchoring residues; in this group of amphiphiles, two tryptophans are connected by alkyl chains or aryl groups. In both cases, however, the antibacterial activity of certain members of each family was apparent. Further, the amphiphiles have been shown to act as adjuvants that increase the potency of such antimicrobials as tetracycline and even to have re-sensitized a tetracycline-resistant E. coli strain to the antibiotic.

show abstract

Synthesis of a membrane-insertable, sodium cation conducting channel: kinetic analysis by dynamic sodium-23 NMR

Cited by 148 publications

References 3 publications

Coordination and transport of alkali metal cations through phospholipid bilayer membranes by hydraphile channels

Coordination and transport of alkali metal cations through phospholipid bilayer membranes by hydraphile channels

The influence of varied amide bond positions on hydraphile ion channel activity

Tryptophan in Membrane-Active Synthetic Antimicrobials

Contact Info

Product

Resources

About