Anti-HIV-1 Activity of Poly(mandelic acid) Derivatives

Abstract

Homo- and heterochiral poly(mandelic acid)s (PMDAs) were synthesized under strongly acidic, mildly acidic, and nonacidic conditions. The water-soluble fractions of these polymers were evaluated with respect to their inhibitory activity against the human immunodeficiency virus (HIV-1). Polymers were prepared via a step-growth mechanism, yielding linear polyesters. The polymers were characterized by CHS elemental microanalysis, X-ray fluorescence (XRF), and FT-IR spectroscopy. Polymers prepared by the three methods have different structures. Both elemental microanalysis and XRF indicated the presence of S in those polymers prepared by treatment with concentrated H2SO4, which were the only ones exhibiting inhibitory and virucidal activity against HIV-1, mediated by their binding to cellular co-receptor binding sites on the virus envelope glycoprotein gp120. Additionally, FT-IR spectroscopy indicated the complete absence of C=O functionality in the H2SO4-prepared PMDA.

Feasibility of Repurposing the Polyanionic Microbicide, PPCM, for Prophylaxis against HIV Transmission during ART

“…The loss of viral integrity suggests an irreversible mechanism of action. The work of Mesquita and coworkers [33] suggests possible irreversible inhibition of HIV-1 (BaL) and HIV-1 (RF) infectivity after pretreatment of immobilized virus with PPCM followed by washing, Further, a structural variant of PPCM inhibits HIV-1 (IIIB) and HIV-1 (BaL) in an irreversible or pseudoirreversible manner [51]. These data are in agreement with the present study.…”

“…Part of the effect may be due to inhibition of viral entry. This occurs by preventing the interaction of the positively charged V3 loop of viral gp120 with negatively charged coreceptors (e.g., heparan sulfate or similar) on target (host) cells [51]. Studies with other polyanionic microbicides (e.g., cellulose sulfate, polystyrene sulfonate, cellulose sulfate phthalate) suggest that relatively high concentrations of these agents may cause gp41 six-helix bundle formation, viral disintegration and rapid loss of infectivity [52].…”

Enhancement of Tg of Poly(l‐lactide) by Incorporation of Biobased Mandelic‐Acid‐Derived Phenyl Groups by Polymerization and Polymer Blending

“…In addition to the biobased nature of ma, the nontoxicity of ma is also attractive, as it is practically used in the current food, cosmetics, and pharmaceutical industries . A homo‐polymer of ma and its derivatives were reported to be active against HIV‐1, but the resultant polymers have insufficient molecular weight for general and engineering applications of polymeric materials. The first high‐molecular‐weight polyester consisting of ma was reported by Baker et al, which is based on ring‐opening polymerization (ROP) of a cyclic diester of meso‐mandelide (mMN).…”

Bacterial bifunctional chorismate mutase-prephenate dehydratase PheA increases flux into the yeast phenylalanine pathway and improves mandelic acid production

“…Prior to that, three studies focused on the production of MA or MA derivatives in Escherichia coli ( Liu et al, 2014 , Müller et al, 2006 , Sun et al, 2011 ). MA finds use in the cosmetic industry and serves as a precursor for the production of pharmaceutically active compounds ( Chang et al, 2007 , Furlenmeier et al, 1976 , Mill et al, 1983 , Nishizawa et al, 1985 , Saravanan and Singh, 1998 , Ward et al, 2007 ). MA production in E. coli and S. cerevisiae was achieved by introducing heterologous hydroxymandelate synthases (HmaS), which convert phenylpyruvate, the precursor of phenylalanine, to MA ( Liu et al, 2014 , Müller et al, 2006 , Reifenrath and Boles, 2018 , Sun et al, 2011 ).…”