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Triazine-bridged bicyclic peptoids as conformationally constrained peptidomimetics are described. Bicyclic peptoids composed of 6-12 peptoid residues (m, n = 3-6) were synthesized in excellent yields using a highly efficient solid-phase synthetic route. 相似文献
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Yeongju Lee Jiwon Heo Hoibin Jeong Kyung Tae Hong Do Hoon Kwon Min Hyeon Shin Misook Oh Ganesh A. Sable G-One Ahn Jun-Seok Lee Hyun Kyu Song Hyun-Suk Lim 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(40):17701-17708
Aberrantly elevated steroid receptor coactivator-1 (SRC-1) expression and activity are strongly correlated with cancer progression and metastasis. Here we report, for the first time, the development of a proteolysis targeting chimera (PROTAC) that is composed of a selective SRC-1 binder linked to a specific ligand for UBR box, a unique class of E3 ligases recognizing N-degrons. We showed that the bifunctional molecule efficiently and selectively induced the degradation of SRC-1 in cells through the N-degron pathway. Importantly, given the ubiquitous expression of the UBR protein in most cells, PROTACs targeting the UBR box could degrade a protein of interest regardless of cell types. We also showed that the SRC-1 degrader significantly suppressed cancer cell invasion and migration in vitro and in vivo. Together, these results demonstrate that the SRC-1 degrader can be an invaluable chemical tool in the studies of SRC-1 functions. Moreover, our findings suggest PROTACs based on the N-degron pathway as a widely useful strategy to degrade disease-relevant proteins. 相似文献
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Here we describe a simple method that allows for rapid and easy sequence determination of cyclic peptoids. The key idea in this strategy is a post-screening "ring-opening" reaction to convert cyclic peptoids selected from a high-throughput screen into linear peptoids, which can be sequenced by tandem mass spectrometry. Thus, there is no need for encoding. 相似文献
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Lee JH Zhang Q Jo S Chai SC Oh M Im W Lu H Lim HS 《Journal of the American Chemical Society》2011,133(4):676-679
There is considerable interest in developing non-peptidic, small-molecule α-helix mimetics to disrupt α-helix-mediated protein?protein interactions. Herein, we report the design of a novel pyrrolopyrimidine-based scaffold for such α-helix mimetics with increased conformational rigidity. We also developed a facile solid-phase synthetic route that is amenable to divergent synthesis of a large library. Using a fluorescence polarization-based assay, we identified cell-permeable, dual MDMX/MDM2 inhibitors, demonstrating that the designed molecules can act as α-helix mimetics. 相似文献
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Bora Kim Hyun-Suk Shin Jung-Ryul Kim Kyung-Soo Lim Seo Hyun Yoon Kyung-Sang Yu Sang-Goo Shin In-Jin Jang Joo-Youn Cho 《Chromatographia》2012,75(11-12):671-677
A simple, rapid and sensitive LC–MS/MS method in positive ion mode was developed and validated to determine CKD-501, lobeglitazone, in human plasma and urine using glipizide as an internal standard (IS). Lobeglitazone is a novel thiazolidinedione (TZDs)-based peroxisome proliferator-activated receptor (PPAR) agonist, used for the management of type-2 diabetes. After mixing the IS, dissolved in acetonitrile, with a plasma or urine sample containing lobeglitazone, 10?μL of supernatant was injected into the LC–MS/MS system. Quantification was performed in the multiple reaction monitoring (MRM) mode using transition of 481.5?→?152.2 (m/z) for lobeglitazone and 446.1?→?321.2 (m/z) for the IS. The method showed good linearity over concentration ranges of 0.5–1,000?ng?mL?1 for plasma and 0.2–250?ng?mL?1 for urine (r 2?≥?0.9996). The mean percent extraction recovery of lobeglitazone was 90.8?% for plasma and 87.3?% for urine, while the recoveries of the IS were greater than 86.4?% for both. The intra-day and inter-day precision of plasma ranged from 1.1 to 3.7 and 2.5 to 3.3?% (RSD), respectively, and the intra- and inter-day precision of urine ranged from 1.5 to 2.7 and 3.2 to 3.5?%, respectively. This method is simple, sensitive, and applicable for the pharmacokinetic study of lobeglitazone in human plasma. Most of the urine concentrations of lobeglitazone were below the LLOQ because the lobeglitazone is extensively metabolized. 相似文献
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Identification and Study of Biomarkers from Novichok-Inhibited Butyrylcholinesterase in Human Plasma
Woo-Hyeon Jeong Jin-Young Lee Kyoung-Chan Lim Hyun-Suk Kim 《Molecules (Basel, Switzerland)》2021,26(13)
To identify biomarkers of ethyl (1-(diethylamino)ethylidene)phosphoramidofluoridate (A234)- or methyl (1-(diethylamino)ethylidene)phosphoramidofluoridate (A232)-inhibited butyrylcholinesterase (BChE), we investigated nonapeptide adducts containing the active site serine, which plays a key role in enzyme activity, using LC-MS/HRMS. Biomarkers were acquired as expected, and they exhibited a significant amount of fragment ions from the inhibiting agent itself, in contrast to the MS2 spectra of conventional nerve agents. These biomarkers had a higher abundance of [M+2H]2+ ions than [M+H]+ ions, making doubly charged ions more suitable for trace analysis. 相似文献
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We report herein the gold-catalyzed tandem hydration/α-ketol rearrangement of 1-alkynylcyclobutanol derivatives, leading to cyclopentanones bearing an α-hydroxy substituted quaternary center. In the presence of water, coordination of gold catalyst onto alkynyl moiety triggers hydration rather than a direct ring expansion, which followed by unprecedented Au-catalyzed α-ketol rearrangement. The details and the scope of this method are presented. 相似文献
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