BIOMAT Database Logo BIOMAT Database Logo

Comprehensive chemical modification interference and nucleotide substitution analysis of an RNA pseudoknot inhibitor to HIV-1 reverse transcriptase. 1995

L Green, and S Waugh, and J P Binkley, and Z Hostomska, and Z Hostomsky, and C Tuerk
NeXagen, Inc., Boulder, CO 80301.

We had previously used in vitro RNA selection techniques to describe a consensus RNA pseudoknot that binds and inhibits HIV-1 reverse transcriptase (HIV-RT). In this work we constructed variants of this consensus pseudoknot in order to evaluate the contributions of individual nucleotide identities and secondary structure to affinity for HIV-RT. We have also used chemical modification of ligand RNAs to corroborate the predicted structure of the pseudoknot, to discover which modifiable groups are protected from chemical attack when bound to HIV-RT, and to find which modifications interfere with binding to HIV-RT. A novel interference study is presented which involves selection of ligands from a pool created by mixed reagent oligonucleotide synthesis in order to rapidly determine allowed substitutions of 2'-OCH3 groups for the usual 2'-OH group in such RNA ligands.

UI MeSH Term Description Entries
D008024 Ligands A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed) Ligand
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009690 Nucleic Acid Conformation The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape. DNA Conformation,RNA Conformation,Conformation, DNA,Conformation, Nucleic Acid,Conformation, RNA,Conformations, DNA,Conformations, Nucleic Acid,Conformations, RNA,DNA Conformations,Nucleic Acid Conformations,RNA Conformations
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D001483 Base Sequence The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence. DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D012194 RNA-Directed DNA Polymerase An enzyme that synthesizes DNA on an RNA template. It is encoded by the pol gene of retroviruses and by certain retrovirus-like elements. EC 2.7.7.49. DNA Polymerase, RNA-Directed,RNA-Dependent DNA Polymerase,Reverse Transcriptase,RNA Transcriptase,Revertase,DNA Polymerase, RNA Directed,DNA Polymerase, RNA-Dependent,RNA Dependent DNA Polymerase,RNA Directed DNA Polymerase
D012313 RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed) RNA, Non-Polyadenylated,Ribonucleic Acid,Gene Products, RNA,Non-Polyadenylated RNA,Acid, Ribonucleic,Non Polyadenylated RNA,RNA Gene Products,RNA, Non Polyadenylated
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human

Related Publications

L Green, and S Waugh, and J P Binkley, and Z Hostomska, and Z Hostomsky, and C Tuerk
The structure of HIV-1 reverse transcriptase complexed with an RNA pseudoknot inhibitor.
August 1998, The EMBO journal,
L Green, and S Waugh, and J P Binkley, and Z Hostomska, and Z Hostomsky, and C Tuerk
Preliminary X-ray diffraction studies of an RNA pseudoknot that inhibits HIV-1 reverse transcriptase.
September 1996, Acta crystallographica. Section D, Biological crystallography,
L Green, and S Waugh, and J P Binkley, and Z Hostomska, and Z Hostomsky, and C Tuerk
Subtype-specific analysis of the K65R substitution in HIV-1 that confers hypersusceptibility to a novel nucleotide-competing reverse transcriptase inhibitor.
January 2015, Antimicrobial agents and chemotherapy,
L Green, and S Waugh, and J P Binkley, and Z Hostomska, and Z Hostomsky, and C Tuerk
Structural Basis of HIV-1 Inhibition by Nucleotide-Competing Reverse Transcriptase Inhibitor INDOPY-1.
November 2019, Journal of medicinal chemistry,
L Green, and S Waugh, and J P Binkley, and Z Hostomska, and Z Hostomsky, and C Tuerk
Identification and characterization of a novel HIV-1 nucleotide-competing reverse transcriptase inhibitor series.
June 2013, Antimicrobial agents and chemotherapy,
L Green, and S Waugh, and J P Binkley, and Z Hostomska, and Z Hostomsky, and C Tuerk
Nontemplated nucleotide addition by HIV-1 reverse transcriptase.
May 2002, Biochemistry,
L Green, and S Waugh, and J P Binkley, and Z Hostomska, and Z Hostomsky, and C Tuerk
Nucleotide modification at the gamma-phosphate leads to the improved fidelity of HIV-1 reverse transcriptase.
January 2005, Nucleic acids research,
L Green, and S Waugh, and J P Binkley, and Z Hostomska, and Z Hostomsky, and C Tuerk
HIV-1 reverse transcriptase inhibitor from Phyllanthus niruri.
November 1992, AIDS research and human retroviruses,
L Green, and S Waugh, and J P Binkley, and Z Hostomska, and Z Hostomsky, and C Tuerk
Structure of HIV-1 reverse transcriptase cleaving RNA in an RNA/DNA hybrid.
January 2018, Proceedings of the National Academy of Sciences of the United States of America,
L Green, and S Waugh, and J P Binkley, and Z Hostomska, and Z Hostomsky, and C Tuerk
Mutations M184V and Y115F in HIV-1 reverse transcriptase discriminate against "nucleotide-competing reverse transcriptase inhibitors".
October 2008, The Journal of biological chemistry,
Copied contents to your clipboard!