62146-62-7Relevant academic research and scientific papers
Bivalent Ligand Aiming Putative Mu Opioid Receptor and Chemokine Receptor CXCR4 Dimers in Opioid Enhanced HIV-1 Entry
Ma, Hongguang,Wang, Huiqun,Li, Mengchu,Barreto-De-Souza, Victor,Reinecke, Bethany A.,Gunta, Rama,Zheng, Yi,Kang, Guifeng,Nassehi, Nima,Zhang, Huijun,An, Jing,Selley, Dana E.,Hauser, Kurt F.,Zhang, Yan
, p. 2318 - 2324 (2020)
A bivalent compound 1a featuring both a mu opioid receptor (MOR) and a CXCR4 antagonist pharmacophore (naltrexone and IT1t) was designed and synthesized. Further binding and functional studies demonstrated 1a acting as a MOR and a CXCR4 dual antagonist wi
Novel bivalent ligands carrying potential antinociceptive effects by targeting putative mu opioid receptor and chemokine receptor CXCR4 heterodimers
Li, Mengchu,Ma, Hongguang,Nassehi, Nima,Pagare, Piyusha P.,Santos, Edna J.,Selley, Dana E.,Stevens Negus, S.,Wang, Huiqun,Zhang, Yan
, (2022/02/01)
The functional interactions between opioid and chemokine receptors have been implicated in the pathological process of chronic pain. Mounting studies have indicated the possibility that a MOR-CXCR4 heterodimer may be involved in nociception and related ph
Platform to Discover Protease-Activated Antibiotics and Application to Siderophore-Antibiotic Conjugates
Boyce, Jonathan H.,Dang, Bobo,Ary, Beatrice,Edmondson, Quinn,Craik, Charles S.,Degrado, William F.,Seiple, Ian B.
, p. 21310 - 21321 (2021/01/11)
Here we present a platform for discovery of protease-activated prodrugs and apply it to antibiotics that target Gram-negative bacteria. Because cleavable linkers for prodrugs had not been developed for bacterial proteases, we used substrate phage to discover substrates for proteases found in the bacterial periplasm. Rather than focusing on a single protease, we used a periplasmic extract of E. coli to find sequences with the greatest susceptibility to the endogenous mixture of periplasmic proteases. Using a fluorescence assay, candidate sequences were evaluated to identify substrates that release native amine-containing payloads. We next designed conjugates consisting of (1) an N-terminal siderophore to facilitate uptake, (2) a protease-cleavable linker, and (3) an amine-containing antibiotic. Using this strategy, we converted daptomycin - which by itself is active only against Gram-positive bacteria - into an antibiotic capable of targeting Gram-negative Acinetobacter species. We similarly demonstrated siderophore-facilitated delivery of oxazolidinone and macrolide antibiotics into a number of Gram-negative species. These results illustrate this platform's utility for development of protease-activated prodrugs, including Trojan horse antibiotics.
From Inhibition to Degradation: Targeting the Antiapoptotic Protein Myeloid Cell Leukemia 1 (MCL1)
Papatzimas, James W.,Gorobets, Evgueni,Maity, Ranjan,Muniyat, Mir Ishruna,Maccallum, Justin L.,Neri, Paola,Bahlis, Nizar J.,Derksen, Darren J.
, p. 5522 - 5540 (2019/06/17)
Protein-protein interactions (PPIs) have emerged as significant targets for therapeutic development, owing to their critical nature in diverse biological processes. An ideal PPI-based target is the protein myeloid cell leukemia 1 (MCL1), a critical prosurvival factor in cancers such as multiple myeloma where MCL1 levels directly correlate to disease progression. Current strategies for halting the antiapoptotic properties of MCL1 revolve around inhibiting its sequestration of proapoptotic factors. Existing inhibitors disrupt endogenous regulatory proteins; however, this strategy actually leads to an increase of MCL1 protein levels. Here, we show the development of hetero-bifunctional small molecules capable of selectively targeting MCL1 using a proteolysis targeting chimera (PROTAC) methodology leading to successful degradation. We have confirmed the involvement of the E3 ligase CUL4A-DDB1 cereblon ubiquitination pathway, making these PROTACs a first step toward a new class of antiapoptotic B-cell lymphoma 2 family protein degraders.
ANTIBACTERIAL SIDEROMYCINS
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Page/Page column 61; 62, (2016/03/13)
A compound, comprising: an Fe(III)-binding and/or Fe(III)-bound siderophore; one or more optional linker covalently bound to the siderophore; and daptomycin covalently bound to the linker, or, if no linker is present, then to the siderophore; or pharmaceu
Novel pseudo[2]rotaxanes constructed by the self-assembly of dibenzyl tetramethylene bis-carbamate derivatives and per-ethylated pillar[5]arene
Xiong, Shuhan,Zhang, Xiaoning,Meng, Lu-Bo,Jiang, Juli,Lin, Chen,Wang, Leyong
supporting information, p. 6504 - 6507 (2015/04/14)
Novel neutral guest molecules, G1-G7, are studied for their host-guest complexation with per-ethylated pillar[5]arene (EtP[5]A). Among them, G1 and G7, dibenzyl tetramethylene bis-carbamate derivatives, are found to afford a novel stable pseudo[2]rotaxane
Synthesis and preliminary investigations into norbornane-based amphiphiles and their self-assembly
Squire, Jennifer S.,Sutti, Alessandra,Durand, Gregory,Conlan, Xavier A.,Henderson, Luke C.
, p. 1895 - 1905 (2013/10/08)
A range of norbornane based amphiphiles, which possess a rigid 'kink' in the centre of amphiphiles, were accessed via a concise four step synthesis. The self-assembly properties of these novel compounds were then investigated and the critical aggregation
Role of the guanidine group in the N-terminal fragment of PTH(1-11)
Caporale, Andrea,Woznica, Iwona,Schievano, Elisabetta,Mammi, Stefano,Peggion, Evaristo
experimental part, p. 1269 - 1275 (2010/07/16)
A series of PTH hybrids containing a diamine [NH2(CH 2) n NH2; n = 4, 5, 6] in the C-terminal position was synthesized based on the H-Aib-Val-Aib-Glu-Ile-Gln-Leu-Nle-His-Gln- Har-NH2 (Har = homoargini
Degradable PEG-folate coated poly(DMAEA-co-BA)phosphazene-based polyplexes exhibit receptor-specific gene expression
Luten,van Steenbergen,Lok,de Graaff,van Nostrum,Talsma,Hennink
, p. 241 - 251 (2008/04/01)
A new cationic biodegradable polyphosphazene was developed, bearing both pendant primary and tertiary amine side groups, poly(2-dimethylaminoethylamine-co-diaminobutane)phosphazene (poly(DMAEA-co-BA)phosphazene). PEG and PEG-folate were coupled to polyple
New fluorescent adenosine A1-receptor agonists that allow quantification of ligand-receptor interactions in microdomains of single living cells
Middleton, Richard J.,Briddon, Stephen J.,Cordeaux, Yolande,Yates, Andrew S.,Dale, Clare L.,George, Michael W.,Baker, Julian G.,Hill, Stephen J.,Kellam, Barrie
, p. 782 - 793 (2008/01/27)
Fluorescence spectroscopy is becoming a valuable addition to the array of techniques available for scrutinizing ligand-receptor interactions in biological systems. In particular, scanning confocal microscopy and fluorescence correlation spectroscopy (FCS) allow the noninvasive imaging and quantification of these interactions in single living cells. To address the emerging need for fluorescently labeled ligands to support these technologies, we have developed a series of red-emitting agonists for the human adenosine A1-receptor that, collectively, are N6-aminoalkyl derivatives of adenosine or adenosine 5′-N-ethyl carboxamide. The agonists, which incorporate the commercially available fluorophore BODIPY [630/650], retain potent and efficacious agonist activity, as demonstrated by their ability to inhibit cAMP accumulation in chinese hamster ovary cells expressing the human adenosine A1-receptor. Visualization and confirmation of ligand-receptor interactions at the cell membrane were accomplished using confocal microscopy, and their suitability for use in FCS was demonstrated by quantification of agonist binding in small areas of cell membrane.
