3392-11-8Relevant articles and documents
Non-covalent binding of tripeptides-containing tryptophan to polynucleotides and photochemical deamination of modified tyrosine to quinone methide leading to covalent attachment
Basari?, Nikola,Erben, Antonija,Mihaljevi?, Branka,Piantanida, Ivo,Sviben, Igor
supporting information, (2021/07/28)
A series of tripeptides TrpTrpPhe (1), TrpTrpTyr (2), and TrpTrpTyr[CH2N(CH3)2 ] (3) were synthesized, and their photophysical properties and non-covalent binding to polynucleotides were investigated. Fluorescent Trp residues (quantum yield in aqueous solvent ΦF = 0.03–0.06), allowed for the fluorometric study of non-covalent binding to DNA and RNA. Moreover, high and similar affinities of 2×HCl and 3×HCl to all studied double stranded (ds)-polynucleotides were found (logKa = 6.0–6.8). However, the fluorescence spectral responses were strongly dependent on base pair composition: the GC-containing polynucleotides efficiently quenched Trp emission, at variance to AT-or AU-polynucleotides, which induced bisignate response. Namely, addition of AT(U) polynu-cleotides at excess over studied peptide induced the quenching (attributed to aggregation in the grooves of polynucleotides), whereas at excess of DNA/RNA over peptide the fluorescence increase of Trp was observed. The thermal denaturation and circular dichroism (CD) experiments supported peptides binding within the grooves of polynucleotides. The photogenerated quinone methide (QM) reacts with nucleophiles giving adducts, as demonstrated by the photomethanolysis (quantum yield ΦR = 0.11–0.13). Furthermore, we have demonstrated photoalkylation of AT oligonucleotides by QM, at variance to previous reports describing the highest reactivity of QMs with the GC reach regions of polynucleotides. Our investigations show a proof of principle that QM precursor can be imbedded into a peptide and used as a photochemical switch to enable alkylation of polynucleotides, enabling further applications in chemistry and biology.
New Class of Selective Estrogen Receptor Degraders (SERDs): Expanding the Toolbox of PROTAC Degrons
Wang, Lucia,Guillen, Valeria S.,Sharma, Naina,Flessa, Kevin,Min, Jian,Carlson, Kathryn E.,Toy, Weiyi,Braqi, Sara,Katzenellenbogen, Benita S.,Katzenellenbogen, John A.,Chandarlapaty, Sarat,Sharma, Abhishek
supporting information, p. 803 - 808 (2018/07/21)
An effective endocrine therapy for breast cancer is to selectively and effectively degrade the estrogen receptor (ER). Up until now, there have been largely only two molecular scaffolds capable of doing this. In this study, we have developed new classes of scaffolds that possess selective estrogen receptor degrader (SERD) and ER antagonistic properties. These novel SERDs potently inhibit MCF-7 breast cancer cell proliferation and the expression of ER target genes, and their efficacy is comparable to Fulvestrant. Unlike Fulvestrant, the modular protein-targeted chimera (PROTAC)-type design of these novel SERDs should allow easy diversification into a library of analogs to further fine-tune their pharmacokinetic properties including oral availability. This work also expands the pool of currently available PROTAC-type scaffolds that could be beneficial for targeted degradation of various other therapeutically important proteins.
4,5-Cis Unsaturated α-GalCer Analogues Distinctly Lead to CD1d-Mediated Th1-Biased NKT Cell Responses
Cui, Yanli,Li, Zhiyuan,Cheng, Zhaodong,Xia, Chengfeng,Zhang, Yongmin
, p. 1209 - 1215 (2015/06/25)
The total synthesis of 4,5-cis unsaturated α-GalCer analogues was achieved, and their immune-response altering activity was assessed in vitro as well as in vivo in mice. Using glycosyl iodide as a glycosyl donor, construction of the sphingosine unit was shortened by four steps and single α-stereoselectivity was achieved in good yield (67%). With regard to the therapeutic use of α-GalCer, the novel analogues (1b and 1c) distinctly induced a Th1-biased cytokine response, avoiding induction of a contradictory response and overstimulation.
