FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2048084660> ?p ?o ?g. }

• W2048084660 abstract "Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FLGuanine-rich nucleic acids can fold into four-stranded G-quadruplex structures which are found in telomeric DNA repeats as well as in sequences in the promoter and other regulatory regions of genes. Small molecules that can selectively bind and stabilize quadruplex structure are of increasing significance as potential anticancer agents. We recently reported a series of novel biaryl polyamides with significant selectively towards G-quadruplex compared to duplex DNA, and modest selectivity between different quadruplex types such as c-kit1, c-kit2 and HT4 (Chemical Commun., 4097, 2009). These molecules were based on a distamycin scaffold but included biaryl building blocks in place of pyrroles to switch preference from duplex to quadruplex DNA. This alteration in shape ensured that the molecules had low affinity for duplex DNA while increasing their interaction with G-quadruplex structure, since the ligands had similar dimensions. We have now synthesized a 34-member second-generation biaryl polyamide library based on the previously obtained structural information. Initial assessment of the G-quadruplex interaction of library members was carried out using a FRET-based melting assay. Two compounds (KN-88 and KN-119) containing hybrid benzofused and biaryl building blocks provided significant selective stabilization of human Telomeric G-quadruplex. At 1 µM they stabilize human Telomeric G-quadruplex by 21 and 18 °C, respectively, while showing insignificant affinity for duplex DNA. FRET competition assays with C-kit quadruplexes and CT DNA further confirmed selective stabilization of telomeric quadruplexes. CD titrations of KN-88 and KN-119 with h-telo, c-kit1 and c-kit2 quadruplex-forming DNA sequences showed concentration-dependent enhancement of major CD signals, and in some cases the ligands induced the folding of a particular quadruplex structure. Kd values for KN-88 and KN-119 for telomeric quadruplex sequences were determined by CD titration and were found to be 2.8 × 106 and 7.0 × 106, respectively. Short-term growth inhibitory experiments against a panel of tumour cell lines (MiaPaCa2, A549, MCF7, HeLa, U87MG and A431) gave low micromolar IC50 values for these two compounds, and significant selectivity for tumour cell lines compared to the non-tumour fibroblast WI38 cell line. Given their low molecular weight, good water solubility and cellular penetration properties, molecules of this type have potential as therapeutic agents and reagents that can selectively probe quadruplex structure and/or selectively down-regulate signaling pathways in cells.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2517. doi:10.1158/1538-7445.AM2011-2517" @default.
• W2048084660 created "2016-06-24" @default.
• W2048084660 creator A5003587331 @default.
• W2048084660 creator A5006960532 @default.
• W2048084660 creator A5015974843 @default.
• W2048084660 creator A5020039469 @default.
• W2048084660 creator A5023160506 @default.
• W2048084660 creator A5024593530 @default.
• W2048084660 creator A5030155743 @default.
• W2048084660 creator A5062744013 @default.
• W2048084660 creator A5069014055 @default.
• W2048084660 creator A5074551287 @default.
• W2048084660 creator A5075532387 @default.
• W2048084660 date "2011-04-15" @default.
• W2048084660 modified "2023-10-08" @default.
• W2048084660 title "Abstract 2517: Hybrid benzofused-biaryl polyamides with selective telomeric G-quadruplex stabilization potential" @default.
• W2048084660 doi "https://doi.org/10.1158/1538-7445.am2011-2517" @default.
• W2048084660 hasPublicationYear "2011" @default.
• W2048084660 type Work @default.
• W2048084660 sameAs 2048084660 @default.
• W2048084660 citedByCount "0" @default.
• W2048084660 crossrefType "proceedings-article" @default.
• W2048084660 hasAuthorship W2048084660A5003587331 @default.
• W2048084660 hasAuthorship W2048084660A5006960532 @default.
• W2048084660 hasAuthorship W2048084660A5015974843 @default.
• W2048084660 hasAuthorship W2048084660A5020039469 @default.
• W2048084660 hasAuthorship W2048084660A5023160506 @default.
• W2048084660 hasAuthorship W2048084660A5024593530 @default.
• W2048084660 hasAuthorship W2048084660A5030155743 @default.
• W2048084660 hasAuthorship W2048084660A5062744013 @default.
• W2048084660 hasAuthorship W2048084660A5069014055 @default.
• W2048084660 hasAuthorship W2048084660A5074551287 @default.
• W2048084660 hasAuthorship W2048084660A5075532387 @default.
• W2048084660 hasConcept C104317684 @default.
• W2048084660 hasConcept C121332964 @default.
• W2048084660 hasConcept C12554922 @default.
• W2048084660 hasConcept C185592680 @default.
• W2048084660 hasConcept C21951064 @default.
• W2048084660 hasConcept C24107716 @default.
• W2048084660 hasConcept C2778301229 @default.
• W2048084660 hasConcept C512185932 @default.
• W2048084660 hasConcept C552990157 @default.
• W2048084660 hasConcept C55493867 @default.
• W2048084660 hasConcept C62520636 @default.
• W2048084660 hasConcept C71240020 @default.
• W2048084660 hasConcept C83762044 @default.
• W2048084660 hasConcept C86803240 @default.
• W2048084660 hasConcept C91881484 @default.
• W2048084660 hasConcept C96305047 @default.
• W2048084660 hasConcept C99611785 @default.
• W2048084660 hasConceptScore W2048084660C104317684 @default.
• W2048084660 hasConceptScore W2048084660C121332964 @default.
• W2048084660 hasConceptScore W2048084660C12554922 @default.
• W2048084660 hasConceptScore W2048084660C185592680 @default.
• W2048084660 hasConceptScore W2048084660C21951064 @default.
• W2048084660 hasConceptScore W2048084660C24107716 @default.
• W2048084660 hasConceptScore W2048084660C2778301229 @default.
• W2048084660 hasConceptScore W2048084660C512185932 @default.
• W2048084660 hasConceptScore W2048084660C552990157 @default.
• W2048084660 hasConceptScore W2048084660C55493867 @default.
• W2048084660 hasConceptScore W2048084660C62520636 @default.
• W2048084660 hasConceptScore W2048084660C71240020 @default.
• W2048084660 hasConceptScore W2048084660C83762044 @default.
• W2048084660 hasConceptScore W2048084660C86803240 @default.
• W2048084660 hasConceptScore W2048084660C91881484 @default.
• W2048084660 hasConceptScore W2048084660C96305047 @default.
• W2048084660 hasConceptScore W2048084660C99611785 @default.
• W2048084660 hasLocation W20480846601 @default.
• W2048084660 hasOpenAccess W2048084660 @default.
• W2048084660 hasPrimaryLocation W20480846601 @default.
• W2048084660 hasRelatedWork W1581625605 @default.
• W2048084660 hasRelatedWork W1982355557 @default.
• W2048084660 hasRelatedWork W2016968345 @default.
• W2048084660 hasRelatedWork W2033008211 @default.
• W2048084660 hasRelatedWork W2043826504 @default.
• W2048084660 hasRelatedWork W2066705481 @default.
• W2048084660 hasRelatedWork W2084889780 @default.
• W2048084660 hasRelatedWork W2086646397 @default.
• W2048084660 hasRelatedWork W2088320323 @default.
• W2048084660 hasRelatedWork W2098446944 @default.
• W2048084660 hasRelatedWork W2129656046 @default.
• W2048084660 hasRelatedWork W2294846964 @default.
• W2048084660 hasRelatedWork W2391713631 @default.
• W2048084660 hasRelatedWork W2483582690 @default.
• W2048084660 hasRelatedWork W2760841927 @default.
• W2048084660 hasRelatedWork W3118820318 @default.
• W2048084660 hasRelatedWork W3136366119 @default.
• W2048084660 hasRelatedWork W1515444902 @default.
• W2048084660 hasRelatedWork W2229784307 @default.
• W2048084660 hasRelatedWork W2230550917 @default.
• W2048084660 isParatext "false" @default.
• W2048084660 isRetracted "false" @default.
• W2048084660 magId "2048084660" @default.
• W2048084660 workType "article" @default.