4KV8

Crystal structure of HIV RT in complex with BILR0355BS

Summary for 4KV8

• Entry DOI: 10.2210/pdb4kv8/pdb
• Related: 1RTH
• Related PRD ID: PRD_900003
• Descriptor: HIV Reverse transcriptase P66, HIV Reverse transcriptase P51, beta-D-fructofuranose-(2-1)-alpha-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: nucleotidyltransferase, transferase
• Biological source: HIV-1 M:B_HXB2R (HIV-1); More
• Cellular location: Gag-Pol polyprotein: Host cell membrane; Lipid-anchor . Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P04585 P04585
• Total number of polymer chains: 2
• Total formula weight: 117479.61

Authors

Coulombe, R. (deposition date: 2013-05-22, release date: 2013-07-31, Last modification date: 2024-02-28)

Primary citation

Laplante, S.R.,Bilodeau, F.,Aubry, N.,Gillard, J.R.,O'Meara, J.,Coulombe, R.
N- versus O-alkylation: Utilizing NMR methods to establish reliable primary structure determinations for drug discovery.
Bioorg.Med.Chem.Lett., 23:4663-4668, 2013

PubMed Abstract: A classic synthetic issue that remains unresolved is the reaction that involves the control of N- versus O-alkylation of ambident anions. This common chemical transformation is important for medicinal chemists, who require predictable and reliable protocols for the rapid synthesis of inhibitors. The uncertainty of whether the product(s) are N- and/or O-alkylated is common and can be costly if undetermined. Herein, we report an NMR-based strategy that focuses on distinguishing inhibitors and intermediates that are N- or O-alkylated. The NMR strategy involves three independent and complementary methods. However, any combination of two of the methods can be reliable if the third were compromised due to resonance overlap or other issues. The timely nature of these methods (HSQC/HMQC, HMBC. ROESY, and (13)C shift predictions) allows for contemporaneous determination of regioselective alkylation as needed during the optimization of synthetic routes.

PubMed: 23809849
DOI: 10.1016/j.bmcl.2013.06.007

Experimental method

X-RAY DIFFRACTION (2.3 Å)