Bioconjugate-Based Molecular Umbrellas

Abstract

Molecular umbrellas are "amphomorphic" compounds that can produce a hydrophobic or a hydrophilic exterior when exposed to a hydrophobic or hydrophilic microenvironment, respectively. Such molecules are composed of two or more facial amphiphiles that are connected to a central scaffold. Molecular umbrellas that have been synthesized to date, using bile acids as umbrella "walls", polyamines such as spermidine and spermine as scaffold material, and L-lysine as "branches", have been found capable of transporting certain hydrophilic peptides, nucleotides, and oligonucleotides across liposomal membranes by passive diffusion. They have also have been shown to increase in the water solubility and hydrolytic stability of a hydrophobic drug, and to exhibit significant antiviral activity. The ability of a fluorescently-labeled molecular umbrella to readily enter live HeLa cells suggests that such conjugates could find use as drug carriers.

Molecular Umbrella–Amphotericin B Conjugates

“…10 When immersed in a hydrophilic environment, these molecules have the potential for creating a hydrophilic exterior. Conversely, when immersed in a lipophilic environment, these same molecules have the potential for producing a lipophilic exterior.…”

Biomaterials made of bile acids

“…The hypothesis of the transportation is illustrated in Figure 16. During this process, the molecular umbrella adopts a shielded conformation and shelters the hydrophilic agent inside the hydrophilic cavity, finally releasing the hydrophilic agent on the other side of the lipid bilayer [92] .…”

“…When the molecules are immersed in aqueous solutions, Figure 15 Di-and tetra-armed umbrellas (X represents the handle of the umbrella that can bind to a desired agent such as oligonucleotides, R = OH, OCH 3 , OCONH 2 or OSO 3 Na) [92] (Reproduced with permission from American Chemical Society).…”

“…A hypothetical mechanism of bilayer transport [92] (Adapted with permission from American Chemical Society).…”

A tryptophan-substituted cholic acid: Expanding the family of labelled biomolecules

“…Tubular structures are also formed by BA molecules substituted with monosaccharide residues through an unusual mechanism involving scrolls as intermediates [25], whereas vesicles are given by some Gemini derivatives [35]. In addition, derivatives with specific surfactant and recognition properties are synthesized to be exploited as protein or drug stabilizers [36,37], dispersing agents for carbon nanotubes [38], efficient anion and carbohydrate receptors [39,40], antimicrobial agents [41,42] and drug carriers [43,44].…”