35418-16-7Relevant articles and documents
Incorporation of cis- and trans -4,5-Difluoromethanoprolines into polypeptides
Kubyshkin, Vladimir S.,Mykhailiuk, Pavel K.,Afonin, Sergii,Ulrich, Anne S.,Komarov, Igor V.
, p. 5254 - 5257 (2012)
Substituted prolines exert diverse effects on the backbone conformation of proteins. Novel difluoro-analogues were obtained by adding difluorocarbene to N-Boc-4,5-dehydroproline methyl ester, which gave the trans-adduct as the sole product with 71% yield. Upon cleavage of the N-protection group the free amino acid decomposed rapidly. Its incorporation into the proline-rich cell-penetrating "sweet arrow peptide" was thus accomplished using a dipeptide strategy. Two building blocks, containing either cis- or trans-4,5-difluoromethanoproline, were obtained by difluorocyclopropanation of the aminoacyl derivatives of 4,5-dehydroproline. The resulting dipeptides were stable under standard conditions of Fmoc solid phase peptide synthesis and, thus, suitable to study conformational effects.
Regioselective reduction of β-enaminoesters
Hussaini, Syed Raziullah,Moloney, Mark G.
, p. 1129 - 1134 (2005)
The regioselective reduction of β-enaminoesters derived from pyroglutamic acid can be readily achieved under mild conditions. Copyright Taylor & Francis, Inc.
An efficient synthetic route tol-γ-methyleneglutamine and its amide derivatives, and their selective anticancer activity
Hossain, Md Imran,Thomas, Ajit G.,Mahdi, Fakhri,Adam, Amna T.,Akins, Nicholas S.,Woodard, Morgan M.,Paris, Jason J.,Slusher, Barbara S.,Le, Hoang V.
, p. 7115 - 7128 (2021/02/26)
In cancer cells, glutaminolysis is the primary source of biosynthetic precursors, fueling the TCA cycle with glutamine-derived α-ketoglutarate. The enhanced production of α-ketoglutarate is critical to cancer cells as it provides carbons for the TCA cycle to produce glutathione, fatty acids, and nucleotides, and contributes nitrogens to produce hexosamines, nucleotides, and many nonessential amino acids. Efforts to inhibit glutamine metabolism in cancer using amino acid analogs have been extensive.l-γ-Methyleneglutamine was shown to be of considerable biochemical importance, playing a major role in nitrogen transport inArachisandAmorphaplants. Herein we report for the first time an efficient synthetic route tol-γ-methyleneglutamine and its amide derivatives. Many of thesel-γ-methyleneglutamic acid amides were shown to be as efficacious as tamoxifen or olaparib at arresting cell growth among MCF-7 (ER+/PR+/HER2?), and SK-BR-3 (ER?/PR?/HER2+) breast cancer cells at 24 or 72 h of treatment. Several of these compounds exerted similar efficacy to olaparib at arresting cell growth among triple-negative MDA-MB-231 breast cancer cells by 72 h of treatment. None of the compounds inhibited cell growth in benign MCF-10A breast cells. Overall,N-phenyl amides andN-benzyl amides, such as3,5,9, and10, arrested the growth of all three (MCF-7, SK-BR-3, and MDA-MB-231) cell lines for 72 h and were devoid of cytotoxicity on MCF-10A control cells;N-benzyl amides with an electron withdrawing group at theparaposition, such as5and6, inhibited the growth of triple-negative MDA-MB-231 cells commensurate to olaparib. These compounds hold promise as novel therapeutics for the treatment of multiple breast cancer subtypes.
The Discovery of Conformationally Constrained Bicyclic Peptidomimetics as Potent Hepatitis C NS5A Inhibitors
Kazmierski, Wieslaw M.,Miriyala, Nagaraju,Johnson, David K.,Baskaran, Sam
supporting information, p. 1649 - 1655 (2021/10/04)
HCV NS5A inhibitors are the backbone of directly acting antiviral treatments against the hepatitis C virus (HCV). While these therapies are generally highly curative, they are less effective in some specific HCV patient populations. In the search for broader-acting HCV NS5A inhibitors that address these needs, we explored conformational restrictions imposed by the [7,5]-azabicyclic lactam moiety incorporated into daclatasvir (1) and related HCV NS5A inhibitors. Unexpectedly, compound 5 was identified as a potent HCV genotype 1a and 1b inhibitor. Molecular modeling of 5 bound to HCV genotype 1a suggested that the use of the conformationally restricted lactam moiety might have resulted in reorientation of its N-terminal carbamate to expose a new interaction with the NS5A pocket located between amino acids P97 and Y93, which was not easily accessible to 1. The results also suggest new chemistry directions that exploit the interactions with the P97-Y93 site toward new and potentially improved HCV NS5A inhibitors.
