96628-67-0Relevant articles and documents
Spectroscopic characterization of interstrand carbinolamine cross-links formed in the 5′-CpG-3′ sequence by the acrolein-derived γ-OH-1,N2-propano-2′-deoxyguanosine DNA adduct
Cho, Young-Jin,Kim, Hye-Young,Huang, Hai,Slutsky, Alvira,Minko, Irina G.,Wang, Hao,Nechev, Lubomir V.,Kozekov, Ivan D.,Kozekova, Albena,Tamura, Pamela,Jacob, Jaison,Voehler, Markus,Harris, Thomas M.,Lloyd, R. Stephen,Rizzo, Carmelo J.,Stone, Michael P.
, p. 17686 - 17696 (2005)
The interstrand N2,N2-dG DNA cross-linking chemistry of the acrolein-derived γ-OH-1,N2-propanodeoxyguanosine (γ-OH-PdG) adduct in the 5′-CpG-3′ sequence was monitored within a dodecamer duplex by NMR spectroscopy, in situ, using a series of site-specific 13C- and 15N-edited experiments. At equilibrium 40% of the DNA was cross-linked, with the carbinolamine form of the cross-link predominating. The cross-link existed in equilibrium with the non-crosslinked N2-(3-oxo-propyl)-dG aldehyde and its geminal diol hydrate. The ratio of aldehyde/diol increased at higher temperatures. The 1,N2-dG cyclic adduct was not detected. Molecular modeling suggested that the carbinolamine linkage should be capable of maintaining Watson-Crick hydrogen bonding at both of the tandem C-G base pairs. In contrast, dehydration of the carbinolamine cross-link to an imine (Schiff base) cross-link, or cyclization of the latter to form a pyrimidopurinone cross-link, was predicted to require disruption of Watson-Crick hydrogen bonding at one or both of the tandem cross-linked C-G base pairs. When the γ-OH-PdG adduct contained within the 5′-CpG-3′ sequence was instead annealed into duplex DNA opposite T, a mixture of the 1,N2-dG cyclic adduct, the aldehyde, and the diol, but no cross-link, was observed. With this mismatched duplex, reaction with the tetrapeptide KWKK formed DNA-peptide cross-links efficiently. When annealed opposite dA, γ-OH-PdG remained as the 1,N2-dG cyclic adduct although transient epimerization was detected by trapping with the peptide KWKK. The results provide a rationale for the stability of interstrand cross-links formed by acrolein and perhaps other αβ-unsaturated aldehydes. These sequence-specific carbinolamine cross-links are anticipated to interfere with DNA replication and contribute to acrolein-mediated genotoxicity.
THERAPEUTIC COMPOSITION OF CURE-PRO COMPOUNDS FOR TARGETED DEGRADATION OF BET DOMAIN PROTEINS, AND METHODS OF MAKING AND USAGE
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Paragraph 0339; 0448, (2022/02/15)
The present application is directed to a therapeutic composition, comprising two precursor compounds (monomers) that are suitable for assembly via two or more reversible covalent bonds. The monomers are polyfunctionalized molecules comprising a bioorthogo
MACROCYCLES AND THEIR USE
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Paragraph 0708; 0711; 0712, (2022/02/06)
The present disclosure relates to macrocyclic compounds, pharmaceutical compositions containing macrocyclic compounds, and methods of using macrocyclic compounds to treat disease, such as cancer.
PROTEIN TYROSINE PHOSPHATASE INHIBITORS AND METHODS OF USE THEREOF
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Page/Page column 326-327, (2021/06/26)
Provided herein are compounds, compositions, and methods useful for inhibiting protein tyrosine phosphatase, e.g, protein tyrosine phosphatase non-receptor type 2 (PTPN2) and/or protein tyrosine phosphatase non-receptor type 1 (PTPN1), and for treating related diseases, disorders and conditions favorably responsive to PTPN1 or PTPN2 inhibitor treatment, e.g, a cancer or a metabolic disease.
