Feng-Wu Liu

Synthesis and in Vitro Antiviral Activities of [(Dihydrofuran-2-yl)oxy]methyl-phosphonate Nucleosides with 2-Substituted Adenine as Base

The synthesis of [(2′,5′‐dihydrofuran‐2‐yl)oxy]methyl‐phosphonate nucleosides with a 2‐substituted adenine base moiety starting from 2‐deoxy‐3,5‐bis‐O‐(4‐methylbenzoyl)‐α‐L‐ribofuranosyl chloride and 2,6‐dichloropurine is described. The key step is the regiospecific and stereoselective introduction of a phosphonate synthon at C(2) of the furan ring. None of the synthesized compounds showed significant in vitro activity against HIV, BVDV, and HBV.

Synthesis of Novel Caged Intramolecular Ketals of β‐C‐Glycopyranosidic Ketones

Novel caged intramolecular ketals of β‐C‐glycosidic ketones were prepared from pyranoses. The structures of the new compounds were elucidated by NMR and HRMS spectral analysis. Preliminary studies revealed that the intramolecular ketal could be used to protect 3‐ and 6‐hydroxyl groups of β‐C‐glycosidic ketones.

Crystal structures of thrombin in complex with chemically modified thrombin DNA aptamers reveal the origins of enhanced affinity.

Abstract Thrombin-binding aptamer (TBA) is a DNA 15-mer of sequence 5′-GGT TGG TGT GGT TGG-3′ that folds into a G-quadruplex structure linked by two T-T loops located on one side and a T-G-T loop on the other. These loops are critical for post-SELEX modification to improve TBA target affinity. With this goal in mind we synthesized a T analog, 5-(indolyl-3-acetyl-3-amino-1-propenyl)-2′-deoxyuridine (W) to substitute one T or a pair of Ts. Subsequently, the affinity for each analog was determined by biolayer interferometry. An aptamer with W at position 4 exhibited about 3-fold increased binding affinity, and replacing both T4 and T12 with W afforded an almost 10-fold enhancement compared to native TBA. To better understand the role of the substituent’s aromatic moiety, an aptamer with 5-(methyl-3-acetyl-3-amino-1-propenyl)-2′-deoxyuridine (K; W without the indole moiety) in place of T4 was also synthesized. This K4 aptamer was found to improve affinity 7-fold relative to native TBA. Crystal structures of aptamers with T4 replaced by either W or K bound to thrombin provide insight into the origins of the increased affinities. Our work demonstrates that facile chemical modification of a simple DNA aptamer can be used to significantly improve its binding affinity for a well-established pharmacological target protein.

1-(2,3-Di-O-acetyl-4-chloro-4-de-oxy-6-O-tosyl-β-d-galactopyranos-yl)propan-2-one methanol 0.25-solvate.

The asymmetric unit of the title solvate, C20H25ClO9S·0.25CH3OH, contains one galactopyranosyl derivative and one-quarter of a methanol solvent molecule. The galactopyranose ring is in the usual 4 C 1 conformation, and the anomeric center of the sugar has a β configuration. The value of θ (3.44°) and the range of torsion angles [or 53.1 (5)–63.0 (5)°] reflect a slight distortion of the 4 C 1 pyranose ring. A minor orientational disorder affects a carbonyl group, which was modeled with two sites for the O atom having occupancies of 0.79 (5) and 0.21 (5). The crystal studied exhibited inversion twinning.