FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2955990437> ?p ?o ?g. }

• W2955990437 endingPage "2752" @default.
• W2955990437 startingPage "2752" @default.
• W2955990437 abstract "Abstract The human telomeric DNA, which consists of tandem repeat sequences of d(TTAGGG)n, plays an important role in cancers and cell aging. Previous studies in human cancer cells have demonstrated DNA G-quadruplex (G4) structure formation in telomeres. G-quadruplexes are four-stranded structures formed in guanine-rich sequences that are held together by guanine-guanine Hoogsteen hydrogen bonding, and G-quadruplex stabilization by small molecules induces tumor cell senescence and apoptosis by repressing telomerase activity and the DNA damage response pathway. Additionally, telomeric-overhang DNA can form biologically relevant higher-order DNA structures containing consecutive G-quadruplexes which provides additional binding sites for small molecules. Thus, telomeric DNA G-quadruplexes have attracted increasing interest as potential drug targets for cancer therapy. Here, we found that a novel platinum (II)-based tripod (Pt-tripod) specifically recognizes the hybrid-1 human telomeric G4, which is formed in the physiologically relevant K+ solution. Pt-tripod strongly represses telomerase activity and exhibits DNA-targeted photodynamic therapy anticancer activity. Using NMR, we show that Pt-tripod binds the hybrid-1 human telomeric G4 over other G-quadruplex structures and dsDNA. We determined solution structures of the 1:1 and the dimeric 4:2 Pt-tripod-hybrid-1 telomeric G4 complexes by NMR. Our 1:1 complex structure shows preferential binding of the Pt-tripod to the 5′-end of hybrid-1 telomeric G4. At higher ligand ratio, Pt-tripod binds to the 3′-end of the hybid-1 G4 and induces an unprecedented dimeric 4:2 structure interlocked by a non-canonical A:A pair at the 3′-end. The specific binding of the Pt-tripod with the hybrid-1 G4 is achieved by unique interaction modes including the π-π stacking, hydrogen bonding, and electrostatic interactions with the loop and flanking segments. The non-planar tertiary amine conformation and three properly sized cationic platinum arms are critical for the specific and strong binding. Our structures provide significant insights into understanding the dynamic binding of small molecules with G-quadruplexes, and a structural basis for future rational anticancer drug design of non-planar small molecules targeting the human telomeric G4. Our studies also provide a potential handle to study the specific protein interactions and biological functions of hybrid-1 human telomeric G4. Citation Format: Wenting Liu, Clement Lin, Zong-wan Mao, Danzhou Yang. Recognition of the hybrid-1 human telomeric G-quadruplex by a platinum(II)-based compound [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2752." @default.
• W2955990437 created "2019-07-12" @default.
• W2955990437 creator A5009870710 @default.
• W2955990437 creator A5014851777 @default.
• W2955990437 creator A5032920140 @default.
• W2955990437 creator A5066357927 @default.
• W2955990437 date "2019-07-01" @default.
• W2955990437 modified "2023-10-12" @default.
• W2955990437 title "Abstract 2752: Recognition of the hybrid-1 human telomeric G-quadruplex by a platinum(II)-based compound" @default.
• W2955990437 doi "https://doi.org/10.1158/1538-7445.am2019-2752" @default.
• W2955990437 hasPublicationYear "2019" @default.
• W2955990437 type Work @default.
• W2955990437 sameAs 2955990437 @default.
• W2955990437 citedByCount "0" @default.
• W2955990437 crossrefType "journal-article" @default.
• W2955990437 hasAuthorship W2955990437A5009870710 @default.
• W2955990437 hasAuthorship W2955990437A5014851777 @default.
• W2955990437 hasAuthorship W2955990437A5032920140 @default.
• W2955990437 hasAuthorship W2955990437A5066357927 @default.
• W2955990437 hasConcept C104317684 @default.
• W2955990437 hasConcept C120665830 @default.
• W2955990437 hasConcept C121332964 @default.
• W2955990437 hasConcept C130614165 @default.
• W2955990437 hasConcept C161624437 @default.
• W2955990437 hasConcept C177336024 @default.
• W2955990437 hasConcept C185592680 @default.
• W2955990437 hasConcept C2778301229 @default.
• W2955990437 hasConcept C512185932 @default.
• W2955990437 hasConcept C552990157 @default.
• W2955990437 hasConcept C55493867 @default.
• W2955990437 hasConcept C71240020 @default.
• W2955990437 hasConcept C83762044 @default.
• W2955990437 hasConcept C94581717 @default.
• W2955990437 hasConceptScore W2955990437C104317684 @default.
• W2955990437 hasConceptScore W2955990437C120665830 @default.
• W2955990437 hasConceptScore W2955990437C121332964 @default.
• W2955990437 hasConceptScore W2955990437C130614165 @default.
• W2955990437 hasConceptScore W2955990437C161624437 @default.
• W2955990437 hasConceptScore W2955990437C177336024 @default.
• W2955990437 hasConceptScore W2955990437C185592680 @default.
• W2955990437 hasConceptScore W2955990437C2778301229 @default.
• W2955990437 hasConceptScore W2955990437C512185932 @default.
• W2955990437 hasConceptScore W2955990437C552990157 @default.
• W2955990437 hasConceptScore W2955990437C55493867 @default.
• W2955990437 hasConceptScore W2955990437C71240020 @default.
• W2955990437 hasConceptScore W2955990437C83762044 @default.
• W2955990437 hasConceptScore W2955990437C94581717 @default.
• W2955990437 hasIssue "13_Supplement" @default.
• W2955990437 hasLocation W29559904371 @default.
• W2955990437 hasOpenAccess W2955990437 @default.
• W2955990437 hasPrimaryLocation W29559904371 @default.
• W2955990437 hasRelatedWork W1964373581 @default.
• W2955990437 hasRelatedWork W1971120464 @default.
• W2955990437 hasRelatedWork W2071737169 @default.
• W2955990437 hasRelatedWork W2078428995 @default.
• W2955990437 hasRelatedWork W2089271846 @default.
• W2955990437 hasRelatedWork W2143754645 @default.
• W2955990437 hasRelatedWork W2807775040 @default.
• W2955990437 hasRelatedWork W2939148429 @default.
• W2955990437 hasRelatedWork W2954844583 @default.
• W2955990437 hasRelatedWork W3037613068 @default.
• W2955990437 hasVolume "79" @default.
• W2955990437 isParatext "false" @default.
• W2955990437 isRetracted "false" @default.
• W2955990437 magId "2955990437" @default.
• W2955990437 workType "article" @default.