Purine nucleosides. XXV. Synthesis of certain derivatives of 5'-amino-5'-deoxy- and 5'-amino-2',5'-dideoxy-.beta.-D-ribofuranosylpurines as purine nucleotide analogs

1969 ◽  
Vol 12 (4) ◽  
pp. 658-662 ◽  
Author(s):  
Mason G. Stout ◽  
Morris J. Robins ◽  
Richard K. Olsen ◽  
Roland K. Robins
Keyword(s):  
Purine Nucleotide ◽  
Nucleotide Analogs ◽  
Derivatives Of

scholarly journals ALKOXYALKYL ESTERS OF NUCLEOTIDE ANALOGS INHIBIT POLYOMAVIRUS DNA REPLICATION AND LARGE T ANTIGEN ACTIVITIES

2020 ◽  
Author(s):  
Nichodemus O. Onwubiko ◽  
Suraya Diaz ◽  
Marcela Krecmerova ◽  
Heinz Peter Nasheuer
Keyword(s):  
Dna Replication ◽  
Tumor Antigens ◽  
Antiviral Agent ◽  
Dna Helicase ◽  
T Antigen ◽  
Nucleotide Analogs ◽  
Large Tumor ◽  
Nucleotide Analog ◽  
Derivatives Of

Polyomavirus-related infections are ubiqutious in immunocompromised individuals and in some cases are intractable and fatal. Due to lack of approved drugs to treat polyomavirus infections, cidofovir, a phosphonate nucleotide analog approved to treat cytomegalovirus infections has been repurposed as anti-polyomavirus agent. Cidofovir has been modified in various ways to improve its efficacies as broad-spectrum antiviral agent. However, the actual mechanisms and targets of cidofovir and its modified derivatives as anti-polyomavirus agents are still under research. Here, polyomavirus large tumor antigens (Tag) activities were identified as the viral target of cidofovir derivatives. The alkoxyalkyl-ester derivatives of cidofovir efficiently inhibit polyomavirus DNA replication in cell-free human extracts and a viral in vitro replication system only utilizing purified proteins. We present evidence that DNA helicase, and DNA binding activities of polyomavirus Tags are diminished in the presence of low concentrations of alkoxyalkyl-ester derivatives of cidofovir suggesting that the inhibition of viral DNA replication is at least in part mediated by inhibiting ssDNA and dsDNA binding activities of Tags. These findings show that the alkoxyalkyl-ester derivatives of cidofovir are effective in vitro without undergoing further conversions and conclude that the inhibitory mechanisms of nucleotide analog-based drugs are more complex than previously believed.

ChemInform Abstract: ANTICOCCIDIAL DERIVATIVES OF 6-AZAURACIL. 1. ENHANCEMENT OF ACTIVITY BY BENZYLATION OF NITROGEN-1. OBSERVATIONS ON THE DESIGN OF NUCLEOTIDE ANALOGS IN CHEMOTHERAPY

1977 ◽  
Vol 8 (34) ◽  
pp. no-no
Author(s):  
B. L. MYLARI ◽  
M. W. MILLER ◽  
H. L. JUN. HOWES ◽  
S. K. FIGDOR ◽  
J. E. LYNCH ◽  
...  
Keyword(s):  
Nucleotide Analogs ◽  
Derivatives Of

Anticoccidial derivatives of 6-azauracil. 1. Enhancement of activity by benzylation of nitrogen-1. Observations on the design of nucleotide analogs in chemotherapy

1977 ◽  
Vol 20 (4) ◽  
pp. 475-483 ◽  
Author(s):  
Banavara L. Mylari ◽  
Max W. Miller ◽  
Harold L. Howes ◽  
Sanford K. Figdor ◽  
John E. Lynch ◽  
...  
Keyword(s):  
Nucleotide Analogs ◽  
Derivatives Of

scholarly journals Role of calcium ions and cyclic nucleotides in regulation of somatotroph functional activity in rats of different age

1994 ◽  
Vol 40 (4) ◽  
pp. 42-45
Author(s):  
V. P. Fedotov ◽  
V. I. Gudoshnikov ◽  
T. V. Mamayeva
Keyword(s):  
Neonatal Period ◽  
Secretory Activity ◽  
Neonatal Rat ◽  
Ionophore A23187 ◽  
Nucleotide Analogs ◽  
Adult Rats ◽  
Clear Cut ◽  
Derivatives Of ◽  
Camp And Cgmp

Somatotropic hormone (STH) biosynthesis and secretion were studied in primary adenohypophyseal cultures of neonatal, prepubertal, and adult rats. It was shown by disc PAAG electrophorqsiS of products synthesized in incubation of neonatal rat hypophyseal cells that L-'4C leucin incorporates predominantly in the STH containing fraction. The share of prelabeled STH secreted into the culture virtually did not depend on the age of animals, this indicating the maturity of mechanisms of basal somatotroph secretion as early as in the neonatal period of development. Ca-regulating agents (ionophore A23187, EGTA) caused quantitatively similar changes of somatotroph secretory activity in cultures of hypophyseal cells from rats of different ages. At the same time, clear-cut age-specific features of stimulating effect of dibutyryl derivatives of cAMP and cGMP on secretion of immunoreactive STH were detected. The results indicate that somatotropic function in neonatal hypophysis is a dominant one and demonstrates increased reactivity to secretogenic action of cyclic nucleotide analogs.

scholarly journals In What Ways Do Synthetic Nucleotides and Natural Base Lesions Alter the Structural Stability of G-Quadruplex Nucleic Acids?

2017 ◽  
Vol 2017 ◽  
pp. 1-45 ◽  
Author(s):  
Janos Sagi
Keyword(s):  
Nucleic Acids ◽  
Building Blocks ◽  
Structural Studies ◽  
Nucleotide Analogs ◽  
Cellular Events ◽  
G Quadruplex ◽  
Natural Base ◽  
The Stability ◽  
Derivatives Of

Synthetic analogs of natural nucleotides have long been utilized for structural studies of canonical and noncanonical nucleic acids, including the extensively investigated polymorphic G-quadruplexes (GQs). Dependence on the sequence and nucleotide modifications of the folding landscape of GQs has been reviewed by several recent studies. Here, an overview is compiled on the thermodynamic stability of the modified GQ folds and on how the stereochemical preferences of more than 70 synthetic and natural derivatives of nucleotides substituting for natural ones determine the stability as well as the conformation. Groups of nucleotide analogs only stabilize or only destabilize the GQ, while the majority of analogs alter the GQ stability in both ways. This depends on the preferredsynorantiN-glycosidic linkage of the modified building blocks, the position of substitution, and the folding architecture of the native GQ. Natural base lesions and epigenetic modifications of GQs explored so far also stabilize or destabilize the GQ assemblies. Learning the effect of synthetic nucleotide analogs on the stability of GQs can assist in engineering a required stable GQ topology, and exploring thein vitroaction of the single and clustered natural base damage on GQ architectures may provide indications for the cellular events.

Synthesis of 8-Amino- and N-Substituted 8-Aminoadenine Derivatives of Acyclic Nucleoside and Nucleotide Analogs

2001 ◽  
Vol 66 (3) ◽  
pp. 517-532 ◽  
Author(s):  
Zlatko Janeba ◽  
Antonín Holý ◽  
Milena Masojídková
Keyword(s):  
Nucleotide Analogs ◽  
One Pot ◽  
Acyclic Nucleoside ◽  
Derivatives Of ◽  
Methanolic Ammonia

8-Aminoadenine derivatives 2 were obtained from 8-bromoadenines 1 in one-pot reaction via 8-azidoadenines. Reaction of 8-bromoadenines 1 with methylamine or dimethylamine in ethanol afforded the corresponding N9-substituted 8-(methylamino)adenines 3 and 8-(dimethylamino)adenines 4. Alkylation of 8-aminoadenine (2a) with diverse alkylation agents afforded N9-substituted 8-aminoadenine derivatives 2, and alkylation of 8-(dimethylamino)adenine (4a) gave mixtures of the corresponding N9-substituted 8-(dimethylamino)adenines 4 and their N3-substituted regioisomers 5. 8,3'-N-Anhydro derivatives 7 were prepared by tosylation of (S)-8-bromo-9-{2-[(diisopropoxyphosphoryl)- methoxy]-3-hydroxypropyl}adenine (1c) followed by treatment with methanolic ammonia or methylamine solution.

Synthesis of Acyclic Nucleoside and Nucleotide Analogs Derived from 6-Amino-7H-purin-8(9H)-one

2000 ◽  
Vol 65 (7) ◽  
pp. 1126-1144 ◽  
Author(s):  
Zlatko Janeba ◽  
Antonín Holý ◽  
Milena Masojídková
Keyword(s):  
Acetic Acid ◽  
Sodium Acetate ◽  
Nucleotide Analogs ◽  
Acyclic Nucleoside ◽  
Derivatives Of

Reaction of 8-bromoadenine derivatives 2 with sodium acetate in acetic acid and cleavage of (S)-7-[(trityloxy)methyl]-7,8-dihydro[1,3]oxazolo[3,2-e]purin-4-amine (12) and diisopropyl (S)-{[(4-amino-8,9-dihydro-7H-[1,3]oxazino[3,2-e]purin-8-yl)oxy]methyl}phosphonate (13a) were used for the synthesis of the corresponding N9-substituted derivatives of 6-amino- 7H-purin-8(9H)-one 3a-3c and 7. Alkylation of 6-amino-7H-purin-8(9H)-one (3a) with diverse alkylation agents afforded the title N9-monosubstituted 3b, 3d and 7a and N7,N9-disub- stituted acyclic nucleoside and nucleotide analogs 6b, 6d and 8a.

Regulatory effects of purine nucleotide analogs with liver glutamate dehydrogenase

1977 ◽  
Vol 482 (2) ◽  
pp. 251-260 ◽  
Author(s):  
I. Lascu ◽  
T. Bârzu ◽  
N.G. Ty ◽  
L.D. Ngoc ◽  
O. Bârzu ◽  
...  
Keyword(s):  
Glutamate Dehydrogenase ◽  
Purine Nucleotide ◽  
Nucleotide Analogs ◽  
Regulatory Effects

Carbocyclic Phosphonate-Based Nucleotide Analogs Related to PMEA II. Racemic cis-Configured Derivatives

1996 ◽  
Vol 61 (5) ◽  
pp. 778-790 ◽  
Author(s):  
Radek Liboska ◽  
Milena Masojídková ◽  
Ivan Rosenberg
Keyword(s):  
Ring Opening ◽  
Nucleoside Analogs ◽  
Mitsunobu Reaction ◽  
Nucleotide Analogs ◽  
Heterocyclic Bases ◽  
Derivatives Of

Racemic N-(cis-2-phosphonomethoxycycloalkyl) derivatives of heterocyclic bases, a novel type of nucleotide analogs related to 9-(2-phosphonomethoxyethyl)adenine (PMEA), are reported. The synthesis of adenine- (6a, 6b), uracil- (6c) and cytosine- (6d) containing carbocyclic phosphonates is based on the reaction of cis-2-hydroxycycloalkyl derivatives of protected nucleobases with diisopropyl tosyloxymethanephosphonate. The starting purine-containing nucleoside analogs 5a-5f were prepared by the Mitsunobu reaction of protected nucleobases with trans-2-benzyloxycycloalkanols, whereas pyrimidine-containing nucleoside analogs 5g-5k were obtained by configurational inversion at C-2' of the corresponding 1-(trans-2-hydroxycycloalkyl)pyrimidines via ring opening of their 2,2'-anhydro derivatives.

Sign in / Sign up

Export Citation Format

Share Document