Novel Asparagine-Derived Lipid Enhances Distearoylphosphatidylcholine Bilayer Resistance to Acidic Conditions

Abstract

A novel asparagine-derived lipid analogue (ALA11,17) bearing a tetrahydropyrimidinone head group and two fatty chains (11 and 17 indicate the lengths of linear alkyl groups) was synthesized in high yield and purity. The thin film hydration of formulations containing 5 mol% or greater ALA11,17 in distearoylphosphatidylcholine (DSPC) generated multilamellar vesicles (MLVs) that remained unaggregated according to optical microscopy, while those formed from DSPC only were highly clustered. The MLVs were processed into unilamellar liposomes via extrusion and characterized by dynamic light scattering (DLS), zeta potential, turbidity, and scanning electron microscopy (SEM) analysis. Results show that the presence of ALA11,17 in DSPC liposomes significantly alters the morphology, colloidal stability, and retention of encapsulated materials in both acidic and neutral conditions. The ability of ALA11,17-hybrid liposomes to encapsulate and retain inclusions under neutral and acidic conditions (pH < 2) was demonstrated by calcein dequenching experiments. DLS and SEM confirmed that ALA11,17/DSPC liposomes remained intact under these conditions. The bilayer integrity observed under neutral and acidic conditions and the likely biocompatibility of these fatty amino acid analogues suggest that ALA11,17 is a promising additive for modulating phosphatidylcholine lipid bilayer properties.

Guinea pig genital tract lipidome reveals in vivo and in vitro regulation of phosphatidylcholine 16:0/18:1 and contribution to Chlamydia trachomatis serovar D infectivity

“…Cholesterol was purchased from Calbiochem (San Diego, CA, USA). Liposome formulations were prepared by lipid film hydration and sonication methods as described previously (Mfuh et al 2011; Li et al 2012a, b). Liposome encapsulated PC 16:0/18:1 or liposomes alone were introduced into Hela and 104C1 cells in triplicate at a concentration of 25 µM/well.…”

Acid-responsive nanospheres from an asparagine-derived amphiphile

“…This construct was previously prepared as an unisolated intermediate that was then acylated with stearoyl chloride to obtain an acid stable lipid (ALA 11 , 17 ). 19 We anticipated that the intermediate could be employed in a triggered-release nanoparticle (NP) since the lipid supported a linear alkyl chain for hydrophobic associations and was observed to degrade under acidic conditions (Fig. 1).…”

“…The major product was assigned the diequatorial 2,4- cis -isomer ( cis -ALA-11; Fig. 2A) based on spectroscopic evidence 23 and prior precedent for the relative stereochemistry of aldehyde-asparagine cyclocondensates, 19,24 which have been ascribed to the expected thermodynamically preferred 1,3-diequatorial orientation of larger substituents in the ring closure step 25b . The equatorial assignment of the 4-CO 2 − group was unequivocally established by vicinal spin-spin coupling constants ( 3 J 4,5α ≈ 12 Hz, and 3 J 4,5β ≈ 5 Hz), in the 1 H NMR spectrum (Fig.…”

Synthesis of (2S,4S)-2-Substituted-3- (3-Sulfanylpropanoyl)-6- Oxohexahydropyrimidine-4-Carboxylic Acids as Potential Antihypertensive Drugs

“…The derivatives of 6-oxohexahydropyrimidine-4-carboxylic acids are used as key intermediates in the synthesis of β-amino acids [12] [13], in the asymmetric cycloaddition reactions [14], in liposomal microencapsulation of biopreparations [15].…”