A novel thrombin binding aptamer containing a G-LNA residue.
In this work, we report the solution structure, thermodynamic studies, and the pharmacological properties of a new modified thrombin binding aptamer (TBA) containing a G-LNA residue, namely d(5'-GGTTGGTGTGGTTGg-3'), where upper case and lower case letters represent DNA and LNA residues, respectively. NMR and CD spectroscopy, as well as molecular dynamics and mechanic calculations, has been used to characterize the three-dimensional structure. The modified oligonucleotide is characterized by a chair-like structure consisting of two G-tetrads connected by three edge-wise TT, TGT, and TT loops. d(5'-GGTTGGTGTGGTTGg-3') is characterized by the same folding of TBA, being two strands parallel to each other and two strands oriented in opposite manner. This led to a syn-anti-syn-anti and anti-syn-anti-syn arrangements of the Gs in the two tetrads. d(5'-GGTTGGTGTGGTTGg-3') possesses an anticoagulant activity, even if decreased with respect to the TBA.
Virno
Ada
A
Dipartimento di Chimica delle Sostanze Naturali, Università degli Studi di Napoli Federico II, via D Montesano 49, Napoli, Italy.
Randazzo
Antonio
A
Giancola
Concetta
C
Bucci
Mariarosaria
M
Cirino
Giuseppe
G
Mayol
Luciano
L
D052157:Aptamers, Nucleotide / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002942:Circular Dichroism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D009711:Nucleotides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011516:Prothrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012266:Ribose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013815:Thermodilution
C434798:2'-O-4'-C-methylene-ribofuranosyl nucleotide; D052157:Aptamers, Nucleotide; D009711:Nucleotides; C081676:thrombin aptamer; D012266:Ribose; D011516:Prothrombin