43 research outputs found
The influence of locked nucleic acid residues on the thermodynamic properties of 2â˛-O-methyl RNA/RNA heteroduplexes
The influence of locked nucleic acid (LNA) residues on the thermodynamic properties of 2â˛-O-methyl RNA/RNA heteroduplexes is reported. Optical melting studies indicate that LNA incorporated into an otherwise 2â˛-O-methyl RNA oligonucleotide usually, but not always, enhances the stabilities of complementary duplexes formed with RNA. Several trends are apparent, including: (i) a 3Ⲡterminal U LNA and 5Ⲡterminal LNAs are less stabilizing than interior and other 3Ⲡterminal LNAs; (ii) most of the stability enhancement is achieved when LNA nucleotides are separated by at least one 2â˛-O-methyl nucleotide; and (iii) the effects of LNA substitutions are approximately additive when the LNA nucleotides are separated by at least one 2â˛-O-methyl nucleotide. An equation is proposed to approximate the stabilities of complementary duplexes formed with RNA when at least one 2â˛-O-methyl nucleotide separates LNA nucleotides. The sequence dependence of 2â˛-O-methyl RNA/RNA duplexes appears to be similar to that of RNA/RNA duplexes, and preliminary nearest-neighbor free energy increments at 37°C are presented for 2â˛-O-methyl RNA/RNA duplexes. Internal mismatches with LNA nucleotides significantly destabilize duplexes with RNA
Amino- and polyaminophthalazin-1(2H)-ones : synthesis, coordination properties, and biological activity
Amino- and polyaminophthalazinones were synthesized by the palladiumâcatalyzed amination (alkyl- and arylamines, polyamines) of 4-bromophthalazinones in good yields. The coordinating properties of selected aminophthalazinones towards Cu(II) ions were investigated and the participation of the nitrogen atoms in the complexation of the metal ion was shown. A biological screening of the potential cytotoxicity of selected synthesized compounds on HT-29 and PC-3 cell lines, as well as on the L-929 cell line, proved that some amino derivatives of phthalazinone show interesting anticancer activities. The detailed synthesis, spectroscopic data, and biological assays are reported
A chemical synthesis of LNA-2,6-diaminopurine riboside, and the influence of 2â˛-O-methyl-2,6-diaminopurine and LNA-2,6-diaminopurine ribosides on the thermodynamic properties of 2â˛-O-methyl RNA/RNA heteroduplexes
Modified nucleotides are useful tools to study the structures, biological functions and chemical and thermodynamic stabilities of nucleic acids. Derivatives of 2,6-diaminopurine riboside (D) are one type of modified nucleotide. The presence of an additional amino group at position 2 relative to adenine results in formation of a third hydrogen bond when interacting with uridine. New method for chemical synthesis of protected 3â˛-O-phosphoramidite of LNA-2,6-diaminopurine riboside is described. The derivatives of 2â˛-O-methyl-2,6-diaminopurine and LNA-2,6-diaminopurine ribosides were used to prepare complete 2â˛-O-methyl RNA and LNA-2â˛-O-methyl RNA chimeric oligonucleotides to pair with RNA oligonucleotides. Thermodynamic stabilities of these duplexes demonstrated that replacement of a single internal 2â˛-O-methyladenosine with 2â˛-O-methyl-2,6-diaminopurine riboside (DM) or LNA-2,6-diaminopurine riboside (DL) increases the thermodynamic stability (ÎÎG°37) on average by 0.9 and 2.3 kcal/mol, respectively. Moreover, the results fit a nearest neighbor model for predicting duplex stability at 37°C. D-A and D-G but not D-C mismatches formed by DM or DL generally destabilize 2â˛-O-methyl RNA/RNA and LNA-2â˛-O-methyl RNA/RNA duplexes relative to the same type of mismatches formed by 2â˛-O-methyladenosine and LNA-adenosine, respectively. The enhanced thermodynamic stability of fully complementary duplexes and decreased thermodynamic stability of some mismatched duplexes are useful for many RNA studies, including those involving microarrays
Contributions of Stacking, Preorganization, and Hydrogen Bonding to the Thermodynamic Stability of Duplexes between RNA and 2â˛- O
Unraveling the structural basis for the exceptional stability of RNA G-quadruplexes capped by a uridine tetrad at the 3Ⲡterminus
Uridine tetrads (U-tetrads) are a structural element encountered in RNA G-quadruplexes, for example, in the structures formed by the biologically relevant human telomeric repeat RNA. For these molecules, an unexpectedly strong stabilizing influence of a U-tetrad forming at the 3' terminus of a quadruplex was reported. Here we present the high resolution solution NMR structure of the r(UGGUGGU)4 quadruplex which, in our opinion, provides an explanation for this stabilization. Our structure features a distinctive, abrupt chain reversal just prior to the 3' uridine tetrad. Similar 'reversed U-tetrads' were already observed in the crystalline phase. However, our NMR structure coupled with extensive explicit solvent molecular dynamics (MD) simulations identifies some key features of this motif, that up to now remained overlooked. These include the presence of an exceptionally stable 2'OH to phosphate hydrogen bond, as well as, the formation of an additional K+ binding pocket in the quadruplex groove
Structural studies on diverse betacyanin classes in matured pigment-rich fruits of <I>Basella alba</I> L. and <I>Basella alba</I> L. var. 'Rubra' (Malabar spinach)
Identification of betacyanins in Basella alba L. and Basella alba L. var. âRubraâ fruits was performed by low- and high-resolution mass spectrometry (LRMS and HRMS) as well as (1)H, (13)C and two-dimensional NMR which revealed hitherto completely not known betacyanin classes in the plant kingdom. Especially, the presence of unique nitrogenous acyl moieties in the structures of the pigments was ascertained by the HRMS Orbitrap detection. Except for detected polar betacyanin glycosylated derivatives, presence of a series of previously not reported pigments such as malonylated betanidin 6-O-β-glusosides with their acyl migration isomers along with the evidence of the 3â˛â˛-hydroxy-butyrylated betacyanins is reported. The first complete NMR data were obtained for novel and principal acylated gomphrenins with hydroxycinnamic acids: 6â˛-O-E-caffeoyl-gomphrenin (malabarin), 6â˛-O-E-sinapoyl-gomphrenin (gandolin), 6â˛-O-E-4-coumaroyl-gomphrenin (globosin) and 6â˛-O-E-feruloyl-gomphrenin (basellin)
Representative UV melting curves 5â˛ACUCCA/5â˛UGGAGU (, 52 ÂľM), 5â˛ACUACCA/5â˛UGGUAGU (, 46 ÂľM), 5â˛ACUCCA/5â˛UGGUAGU (, 51 ÂľM) and 5â˛AUCA/5â˛UGGUAGU (, 51 ÂľM)
<p><b>Copyright information:</b></p><p>Taken from "The influence of locked nucleic acid residues on the thermodynamic properties of 2â˛-O-methyl RNA/RNA heteroduplexes"</p><p>Nucleic Acids Research 2005;33(16):5082-5093.</p><p>Published online 9 Sep 2005</p><p>PMCID:PMC1201327.</p><p>Š The Author 2005. Published by Oxford University Press. All rights reserved</p> Note that sequence 1 has an AC mismatch in the middle