Summary information and primary citation
- PDB-id
- 4rt2; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- transferase-DNA
- Method
- X-ray (1.92 Å)
- Summary
- Ternary complex crystal structure of DNA polymerase beta with (alpha,beta)-ch2-(beta,gamma)-nh-dttp
- Reference
- Kadina AP, Kashemirov BA, Oertell K, Batra VK, Wilson SH, Goodman MF, McKenna CE (2015): "Two Scaffolds from Two Flips: (alpha, beta)/(beta, gamma) CH2/NH "Met-Im" Analogues of dTTP." Org.Lett., 17, 2586-2589. doi: 10.1021/acs.orglett.5b00799.
- Abstract
- Novel α,β-CH2 and β,γ-NH (1a) or α,β-NH and β,γ-CH2 (1b) "Met-Im" dTTPs were synthesized via monodemethylation of triethyl-dimethyl phosphorimido-bisphosphonate synthons (4a, 4b), formed via a base-induced [1,3]-rearrangement of precursors (3a, 3b) in a reaction with dimethyl or diethyl phosphochloridate. Anomerization during final bromotrimethylsilane (BTMS) deprotection after Mitsunobu conjugation with dT was avoided by microwave conditions. 1a was 9-fold more potent in inhibiting DNA polymerase β, attributed to an NH-group interaction with R183 in the active site.
