30189-48-1Relevant articles and documents
Synthesis, molecular modeling and functional evaluation of a GnRH antagonist
Asghari, S. Mohsen,Balalaie, Saeed,Fathi Vavsari, Vaezeh,Ghassempour, Alireza,Golmohammadi, Farhad,Panahi Kokhdan, Esmaeel,Shakeri, Pegah
, (2022/01/20)
In the present study, a series of novel Trp-Pro-Val containing peptides were prepared via solid-phase synthesis, and their structures were cyclized by a disulfide bridge, or modified by adding heterocycles of pyrazine, pyroglutamic acid, and 1,3,4-oxadiaz
Targeting RECQL5 Functions, by a Small Molecule, Selectively Kills Breast Cancer in Vitro and in Vivo
Chakraborty, Saikat,Dutta, Kartik,Gupta, Pooja,Das, Anubrata,Das, Amit,Ghosh, Sunil Kumar,Patro, Birija Sankar
, p. 1524 - 1544 (2021/02/16)
Clinical and preclinical data reveal that RECQL5 protein overexpression in breast cancer was strongly correlated with poor prognosis, survival, and therapeutic resistance. In the current investigation, we report design, synthesis, and specificity of a small molecule, 4a, which can preferentially kill RECQL5-expressing breast cancers but not RECQL5 knockout. Our stringent analysis showed that compound 4a specifically sensitizes RECQL5-expressing cancers, while it did not have any effect on other members of DNA RECQL-helicases. Integrated approaches of organic synthesis, biochemical, in silico molecular simulation, knockouts, functional mutation, and rescue experiments showed that 4a potently inhibits RECQL5-helicase activity and stabilizes RECQL5-RAD51 physical interaction, leading to impaired HRR and preferential killing of RECQL5-expressing breast cancer. Moreover, 4a treatment led to the efficient sensitization of cisplatin-resistant breast cancers but not normal mammary epithelial cells. Pharmacologically, compound 4a was orally effective in reducing the growth of RECQL5-expressing breast tumors (human xenograft) in NUDE-mice with no appreciable toxicity to the vital organs.
Efficient synthesis of novel conjugated 1,3,4-oxadiazole-peptides
Golmohammadi, Farhad,Balalaie, Saeed,Hamdan, Fatima,Maghari, Shokoofeh
supporting information, p. 4344 - 4351 (2018/03/21)
We were interested in the design and synthesis of novel bioisosteric analogues of leuprolide acetate containing the oxadiazole moiety at the C- or N-terminal of the peptide. An efficient approach for the synthesis of 2-amino-1,3,4-oxadiazoles through the reaction of hydrazide with ammonium thiocyanate and desulfurization reaction of the thiosemicarbazides using different coupling reagents was employed. These compounds are bioisosteres of the amide bond. Furthermore, the coupling of 2-amino-1,3,4-oxadiazoles at the C-terminal of leuprolide analogues was carried out, using a coupling reagent in the solution phase. On the other hand, the addition of a 2-amino-1,3,4-oxadiazole to the N-terminal of the peptide sequence was carried out through the reaction of the 2-amino-1,3,4-oxadiazole with succinic anhydride that led to the formation of a carboxylic acid moiety. Addition of the synthesized oxadiazole containing carboxylic acid to the peptide sequence was performed using a coupling reagent and on the surface of the resin. The synthesized peptides containing the oxadiazole moiety at the C- or N-terminal of the peptide sequence are peptidomimetics of leuprolide acetate. All of the synthesized peptides were purified using preparative HPLC and their structures were confirmed using HR-MS (ESI).
