Synthesis and antiretroviral activity of phospholipid analogs of azidothymidine and other antiviral nucleosides.

Hostetler, Karl Y.; Stuhmiller, Louise M.; Lenting, H.B.M.; Bosch, H. van den; Dd, Richman

doi:10.1016/s0021-9258(19)39299-3

Cited by 103 publications

(36 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During the past few years we and other research groups have become interested in lipids bearing a covalently attached nucleobase. − These compounds are of interest because they link the chemistry of lipids with the chemistry of nucleic acids, in addition to having therapeutical relevance. − Particularly attractive are liposomes from phosphatidyl nucleosides, obtained from complementary nucleobases, e.g., (1,2-dioleoyl- sn -glycero(3)phosphatidyl)-adenosine and (1,2-dioleoyl- sn -glycero(3)phosphatidyl)-uridine, because they permit one to question whether and to what extent they are able to display the complementary binding and recognition properties that are characteristic of the linear DNA macromolecules. The work describing these binding properties with liposomes was published elsewhere .…”

Section: Introductionmentioning

confidence: 99%

Spectroscopy and Recognition Chemistry of Micelles from Monoalkyl Phosphoryl Nucleosides

Heiz¹,

Rädler²,

Luisi³

1998

J. Phys. Chem. B

View full text Add to dashboard Cite

We describe the properties of aqueous micelles obtained from n-alkyl phosphoryl nucleosides, in particular n-hexadecylphosphoryladenosine (C16-AMP), uridine (C16-UMP), and -cytidine (C16-CMP). These compounds were obtained enzymatically. It is shown that each of these compounds form micelles spontaneously in water with a critical micelle concentration in the range of 20−35 μM and an aggregation number of 69, which indicates that the chemical structure of the bases has no significant influence on the aggregation behavior. UV-absorption and circular dichroic measurements suggest that the nucleoside is in an aqueous environment, as expected from the amphiphilic character of the compounds. UV absorption suggests a moderate self-stacking among the bases for each type of micelle. When we mixed micelles bearing complementary bases with each other (e.g., C16-AMP with C16-CMP), a weak hypochromic effect was observed, which can be taken as an indication of complementary base interaction. However, such electronic perturbation was observed also in noncomplementary bases, e.g., when C16-CMP micelles were mixed with C16-UMP micelles. These micelle data are compared with the corresponding data obtained with liposomes obtained from phosphatidyl nucleosides. All together, these data illustrate a novel type of polymeric nucleoside interaction with which no covalent bonds form among the monomers, and in which the nucleobases are distributed as a supramolecular spherical aggregate.

show abstract

Section: Introductionmentioning

confidence: 99%

Spectroscopy and Recognition Chemistry of Micelles from Monoalkyl Phosphoryl Nucleosides

Heiz¹,

Rädler²,

Luisi³

1998

J. Phys. Chem. B

View full text Add to dashboard Cite

show abstract

“…In a previous paper 1a we have reported on the behavior of liposomes obtained from phosphatidyl nucleosides, in particular 5′-(1-palmitoyl-2-oleoyl-sn-glycero(3)phospho)cytidine (1) and 5′-(1-palmitoyl-2-oleoyl-sn-glycero(3)phospho)inosine (2), which were obtained enzymatically from the corresponding phosphatidylcholines and nucleosides.…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, phosphatidyl nucleosides and the corresponding liposomes appear to be interesting from the biomedical point of view. 2,3 In order to display the information and recognition properties typical of nucleic acids, the bases of the phosphatidyl nucleosides in the liposomes must be available for binding. Since cytidine or inosine is part of the polar headgroup, one may expect that it is exposed to water.…”

Section: Introductionmentioning

confidence: 99%

“…The interest in this type of supramolecular lipid aggregates is twofold: On the one hand, they permit one to investigate whether and to what extent the chemical and binding properties of nucleic acids can be expressed also on the spherical structure of the liposomeswhether, for example, complementary base-pairing recognition also works at this novel structural level. On the other hand, phosphatidyl nucleosides and the corresponding liposomes appear to be interesting from the biomedical point of view. , …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Liposomes from Phosphatidyl Nucleosides: An NMR Investigation

et al. 1997

View full text Add to dashboard Cite

We describe an NMR analysis of liposomes obtained from two phosphatidyl nucleosides, namely 5′-(1-palmitoyl-2-oleoyl-sn-glycero(3)phospho)cytidine (1) and 5′-(1-palmitoyl-2-oleoyl-sn-glycero(3)phospho)-inosine (2). This analysis is mostly based on 1D-and 2D-1 H-NMR at high field and is aimed at investigating intramolecular interactions between groups within the same lipid molecule and intermolecular interactions between neighboring lipid molecules in the liposome aggregate. Particular care was taken to choose mixing times which reduce the possibility of spin diffusion effects. The presence of particular cross peaks in 2D-1 H-NOESY experiments permits us to assess the presence of syn-and anti-conformations of the aromatic head groups both in the monomeric nucleotides and in the liposomes. The lack of any particular ring effect in liposomes suggests that no stacking interactions of the nucleobases are present. On the other hand, the presence of other distinct cross peaks indicates short interatomic distances between a given aromatic base and the sugar moiety of an adjacent phosphatidyl nucleoside headgroup. These data permit one to draw a structural model of the liposome surface which accounts for the poor binding characteristics of phosphatidyl nucleoside liposomes toward complementary oligonucleotide strands.

show abstract

“…Liponucleoside conjugates are compounds of high significance in some areas of medicinal chemistry, showing antineoplastic − and antiviral activity. , The presence of a lipophilic moiety in the molecular structure of these compounds allows them to permeate intact cells better than free nucleosides, and in effect, the conjugation of hydrophobic groups to pharmacologically active nucleosides has shown its efficacy at markedly improving their activity. ,, …”

Section: Introductionmentioning

confidence: 99%

Chemoenzymatic Synthesis of Lysophosphatidylnucleosides

1998

View full text Add to dashboard Cite

5‘-O-Lysophosphatidylnucleosides [5‘-O-(1-O-acyl-sn-glycero-3-phosphoryl)nucleosides] were obtained by a two-step chemoenzymatic synthesis. 5‘-O-(sn-Glycero-3-phosphoryl)nucleosides (5‘-GPNs) were first prepared from a phosphoramidite of 1,2-O-isopropylidene-sn-glycerol and appropriately protected nucleosides, applying the phosphoramidite methodology on the solid phase or in solution. In a following step, the regioselective acylation at the C-1 hydroxyl of the glycerol moiety of 5‘-GPNs was achieved by a lipase-catalyzed transacylation with activated fatty acid esters in organic solvent. Some deoxyribo- and ribonucleosides, as well, were converted into the corresponding lysophosphatidyl derivatives utilizing either saturated or unsaturated fatty acid esters with different length alkyl chains. The synthesis was also applied to the preparation of O-(1-O-palmitoyl-sn-glycero-3-phosphoryl) conjugates of Acyclovir and AZT, of potential pharmacological interest.

show abstract

Synthesis and antiretroviral activity of phospholipid analogs of azidothymidine and other antiviral nucleosides.

Cited by 103 publications

References 36 publications

Spectroscopy and Recognition Chemistry of Micelles from Monoalkyl Phosphoryl Nucleosides

Spectroscopy and Recognition Chemistry of Micelles from Monoalkyl Phosphoryl Nucleosides

Liposomes from Phosphatidyl Nucleosides: An NMR Investigation

Chemoenzymatic Synthesis of Lysophosphatidylnucleosides

Contact Info

Product

Resources

About