Antiviral Activity of Synthetic Aminopyrrolic Carbohydrate Binding Agents: Targeting the Glycans of Viral gp120 to Inhibit HIV Entry

Abstract

The binding abilities of a set of structurally related aminopyrrolic synthetic receptors for mannosides, endowed with antimycotic activity against yeast and yeast-like pathogens bearing mannoproteins on their cell surface, have been investigated towards the highly mannosylated gp120 and gp41 glycoproteins of the HIV envelope. A pronounced binding interaction with both glycoproteins was observed by SPR for most of the investigated compounds. Comparison of their binding properties towards the glycoproteins with their binding affinities toward mannosides revealed a direct correlation, supporting their role as carbohydrate binding agents (CBAs). Cytostatic activity studies revealed antiproliferative activity dependent on the nature and the structure of compounds. Antiviral activity studies against a broad panel of DNA and RNA viruses showed inhibitory effect against HIV infection of the T-lymphocyte CEM cell line for two compounds, suggesting antiviral activity similar to other CBAs, such as the nonpeptidic pradimicin antibiotics.

The challenges of glycan recognition with natural and artificial receptors

“…100 Analogous aminopyrrolic derivatives were able to bind the highly mannosylated HIV virial envelope glycoproteins gp120 and gp41, as evidenced by SPR studies, as well as showing antiviral activity against HIV infection of T-lymphocyte CEM cells. 101 Although the aforementioned derivatives showed good binding properties in polar organic media, solubility in water was very poor, limiting their application in aqueous systems. Receptors with impressive binding abilities in water were obtained by developing polycyclic cages where parallel aromatic surfaces were connected via water-solubilising spacers.…”

Synthesis and Binding of Mannose‐Specific Synthetic Carbohydrate Receptors

“…The peak shifts are attributed to the change in chemical environment as a result of reversible supramolecular association between the glycan and the SCR that is occurring in the fast exchange regime. When involved in C−H⋅⋅⋅π interactions with aryl rings of SCRs, protons shift upfield,–– so these results suggest that these Hs do not form C−H⋅⋅⋅π interactions with SCR019 . In contrast, the peaks corresponding to H 1 and H 5 of β‐Man both shift upfield 0.04 ppm, upon association, suggesting the formation of C−H⋅⋅⋅π interactions with the aromatic rings of SCR019 , which is corroborated by molecular modeling (Figure S80).…”

A Biomimetic Synthetic Receptor Selectively Recognising Fucose in Water

“…[3,4] Although widely used as tools in glycobiology and diagnostics,t he development of lectins as therapeutics is hampered by their proteic nature. [5][6][7] Biomimetic synthetic receptors for carbohydrates, often called "synthetic lectins", [8][9][10] developed to mimic the functiono fl ectins in specific recognition events, [11][12][13][14] are small molecules that exploit noncovalent interactions usedb y their natural counterparts to bind saccharides. [15,16] Although in recent decades significant efforts have been dedicatedt ot he design of biomimetic receptors for carbohydrates, [17][18][19][20] at present, only af ew examples of structures effective in the competitive aqueous environmenth ave been reported.…”