- Metal-ion-mediated base pairing between natural nucleobases and bidentate 3,5-dimethylpyrazolyl-substituted purine ligands
-
The potential of three modified purine bases, namely, 6-(3,5-dimethylpyrazol-1-yl)purine, 2-(3,5-dimethylpyrazol-1-yl)hypoxanthine, and 2-(3,5-dimethylpyrazol-1-yl)adenine, for metal-ion-mediated base pairing within an oligonucleotide environment has been investigated. The respective modified nucleosides were incorporated in the middle of 9-mer 2′-O-methyl oligonucleotides and the hybridization of these modified oligonucleotides with their unmodified counterparts studied by UV and CD spectrometry in the absence and presence of Cu2+ or Zn2+. All of the modified oligonucleotides formed more stable duplexes in the presence of divalent metal ions than in the absence thereof, but with different preferences for the complementary oligonucleotide. The oligonucleotide incorporating 2-(3,5-dimethylpyrazol-1-yl)hypoxanthine readily accepted any of the natural nucleobases opposite to this modified base regardless of whether Cu2+ or Zn2+ was used as the bridging metal ion. The other two oligonucleotides, on the other hand, were much more discriminating, exhibiting markedly elevated Tm values only in the presence of Cu2+ and only when certain natural nucleobases were paired with the modified one. The origin of the selectivity (or promiscuity) of the metal-ion-mediated base pairing is discussed in terms of the ability of the modified nucleobases, as well as their natural counterparts, to serve as anionic ligands.
- Taherpour, Sharmin,Golubev, Oleg,L?nnberg, Tuomas
-
-
Read Online
- 6-Hydrazinoadenosine compounds with A2A adenosine receptor agonist activity
-
The present disclosure provides 6-hydrazinoadenosine having A2A adenosine receptor agonistic activity represented by general formula (I) and a derivative thereof, and a pharmaceutical composition containing same. The compound and composition can be used as an A2A adenosine receptor agonist as a medicament.
- -
-
Page/Page column 15
(2022/03/02)
-
- ADENOSINE ANALOG AND ITS USE IN REGULATING THE CIRCADIAN CLOCK
-
Provided are a kind of nucleoside analogue compounds, and compositions comprising these compounds and pentostatin, their use for modulating circadian rhythm, preferably, for shifting circadian phase, and methods for modulating circadian rhythm, preferably, for shifting circadian phase via these compounds or the compositions.
- -
-
Paragraph 0263-0265
(2018/08/12)
-
- Anti-malarial activity of N6-modified purine analogues
-
Plasmodium falciparum causes one of the deadliest forms of malaria and resistance to the currently available drugs makes it imperative to develop new, safe and potent drugs. Parasites such as P. falciparum are unable to synthesise purines de novo and to t
- Too, Kathleen,Brown, Daniel M.,Bongard, Emily,Yardley, Vanessa,Vivas, Livia,Loakes, David
-
p. 5551 - 5562
(2008/03/14)
-
- ANTIPARASITIC COMPOUNDS AND COMPOSITIONS
-
Disclosed is use of a compound having a structure according to general formula (I) defined below, in the manufacture of a medicament to treat and/or prevent a parasitic infection or infestation in a mammalian subject wherein X1 = N or CH or C=O (X2 = NH) or C=S (X2 = NH) or C-OR1 or C-halogen or C-azide; X2 = N or CR1 or C-halogen or CS(O)nR1 where n = 0-2 or a (C)m linker where m = 1-3 between X2 and X6 or C-X5X6 (in which case X5X6 at C6 (purine numbering) is replaced by H or NHR1 or O or OR1 or S or SR1); X3 = N or CH or C-NO2; X4 = N or CH or C-NO2 or C-NR1R2 or an amidine derivative or a guanidinium derivative; X5 = O or NR1 or CR1R2; X6 = OR1 or O-acyl or 0-S(O)nR1 or NR1R2 or NH-acyl or N(Acyl)2 or NH-OS(O)2R1 or NH-S(O)nR1 where n = 0-2 or a hydrazone derivative or an oxime derivative, but if X5 = O, X6 cannot = O or X5X6 is an amidine or an N-substituted pyridine or substituted guanidine; Y = H or NH2 or NR1R2 or -O (X3 = NH) or OR1 or F or Cl or Br or I or CR1R2R3 or S(O)nR1 where n = 0-2 or azide or X5X6 (in which case X5X6 at C6 (purine numbering) is replaced by H or NHR1 or O or OR1 or S or SR1); R1, R2, R3 are independently selected from the group consisting of H or (optionally substituted), alkyl, alkenyl or alkynyl or aryl or aralkyl where the substituents may be selected from H, OH, NH2, halogen, N3, CN, CHO, COOR', C0NR'2, OR, NE'2, SR', NR'NR'2, NR'OR', NO2 and R' is alkyl, alkenyl, alkynyl, aralkyl, acyl, sulfonyl; Z = H or substituted (alkyl or alkenyl or alkynyl or aralkyl) or a sugar derivative of general formula (II) in the β-configuration where: B is the nucleobase from Formula (I); X7 = CH2 or O or NR1 or S; R4 = H or OH or OR1 or halogen or azide or a phosphate derivative; R5 = H or F or CH3; R6 = H or OH or OR1 or halogen or azide or a phosphate derivative; and R7 = H or halogen or R1 or a derivative of an amino acid or PO3H2 or P2O6H3 or P3O9H4 or a methylene derivative of P2O6H3 or P3O9H4 or a masked phosphate or a phosphonate derivative (5'-O replaced with CH2).
- -
-
Page/Page column 35; 36
(2010/11/29)
-
- PURINE DERIVATIVES AS ADENOSINE A1 RECEPTOR AGONISTS AND METHODS OF USE THEREOF
-
The invention relates to Purine Derivatives, compositions comprising an effective amount of a Purine Derivative; and methods for reducing an animal’s rate of metabolism, protecting an animal’s heart against myocardial damage during cardioplegia; or for treating or preventing a cardiovascular disease, a neurological disorder, an ischemic condition, a reperfusion injury, obesity, or wasting disease, or diabetes, comprising administering an effective amount of a Purine Derivative to an animal in need thereof.
- -
-
Page/Page column 135
(2008/06/13)
-