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Medicinal and Pharmaceutical Chemistry Commons™
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- Breast cancer (2)
- ABIN-1 (1)
- Airway smooth muscle (1)
- Alphavirus (1)
- Antiproliferative assay (1)
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- Antiviral agents (1)
- CD44 (1)
- Camptothecin (1)
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- Cell-penetrating peptide (1)
- Chikungunya virus (1)
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- Corticosteroids (1)
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- Docetaxel (1)
- Doxorubicin (1)
- Extra domain B (1)
- Fibronectin (1)
- Fmoc/tBu (1)
- G protein-coupled receptors (1)
- Gout (1)
- Hyaluronic acid (1)
- Hydrophobic modification (1)
- Lipopolymers (1)
- MCF-7 (1)
- MSU (1)
- Membrane glucocorticoid receptor (1)
Articles 1 - 10 of 10
Full-Text Articles in Medicinal and Pharmaceutical Chemistry
Glucocorticoids Rapidly Activate Camp Production Via GΑs To Initiate Non-Genomic Signaling That Contributes To One-Third Of Their Canonical Genomic Effects, Francisco J. Nuñez, Timothy B. Johnstone, Maia L. Corpuz, Austin G. Kazarian, Nicole N. Mohajer, Omar Tliba, Reynold A. Pannettieri Jr., Cynthia J. Koziol-White, Moom Roosan, Rennolds S. Ostrom
Glucocorticoids Rapidly Activate Camp Production Via GΑs To Initiate Non-Genomic Signaling That Contributes To One-Third Of Their Canonical Genomic Effects, Francisco J. Nuñez, Timothy B. Johnstone, Maia L. Corpuz, Austin G. Kazarian, Nicole N. Mohajer, Omar Tliba, Reynold A. Pannettieri Jr., Cynthia J. Koziol-White, Moom Roosan, Rennolds S. Ostrom
Pharmacy Faculty Articles and Research
Glucocorticoids are widely used for the suppression of inflammation, but evidence is growing that they can have rapid, non-genomic actions that have been unappreciated. Diverse cell signaling effects have been reported for glucocorticoids, leading us to hypothesize that glucocorticoids alone can swiftly increase the 3′,5′-cyclic adenosine monophosphate (cAMP) production. We found that prednisone, fluticasone, budesonide, and progesterone each increased cAMP levels within 3 minutes without phosphodiesterase inhibitors by measuring real-time cAMP dynamics using the cAMP difference detector in situ assay in a variety of immortalized cell lines and primary human airway smooth muscle (HASM) cells. A membrane- impermeable glucocorticoid showed …
Design And Biological Evaluation Of Colchicine-Cd44-Targeted Peptide Conjugate In An In Vitro Model Of Crystal Induced Inflammation, Khalid A. Zoghebi, Emira Bousoik, Keykavous Parang, Khaled A. Elsaid
Design And Biological Evaluation Of Colchicine-Cd44-Targeted Peptide Conjugate In An In Vitro Model Of Crystal Induced Inflammation, Khalid A. Zoghebi, Emira Bousoik, Keykavous Parang, Khaled A. Elsaid
Pharmacy Faculty Articles and Research
Gout is an inflammatory arthritis due to the joint deposition of monosodium urate (MSU) crystals. Phagocytosis of MSU crystals by tissue macrophages results in the generation of reactive oxygen species (ROS) and production of inflammatory cytokines and chemokines. Colchicine use in gout is limited by severe toxicity. CD44 is a transmembrane glycoprotein that is highly expressed in tissue macrophages and may be involved in gout pathogenesis. The P6 peptide is a 20-amino acid residue peptide that binds to CD44. We hypothesized that the conjugation of colchicine to the P6 peptide would reduce its off-target cytotoxicity while preserving its anti-inflammatory effect. …
A Systematic Comparison Of Lipopolymers For Sirna Delivery To Multiple Breast Cancer Cell Lines: In Vitro Studies, Hamidreza Montazeri Aliabadi, Remant Bahadur Kc, Emira Bousoik, Ashley Barbarino, Bindu Thapa, Melissa Coyle, Parvin Mahdipoor, Hasan Uludağ
A Systematic Comparison Of Lipopolymers For Sirna Delivery To Multiple Breast Cancer Cell Lines: In Vitro Studies, Hamidreza Montazeri Aliabadi, Remant Bahadur Kc, Emira Bousoik, Ashley Barbarino, Bindu Thapa, Melissa Coyle, Parvin Mahdipoor, Hasan Uludağ
Pharmacy Faculty Articles and Research
Small interfering RNA (siRNA) therapy is a promising approach for treatment of a wide range of cancers, including breast cancers that display variable phenotypic features. To explore the general utility of siRNA therapy to control aberrant expression of genes in breast cancer, we conducted a detailed analysis of siRNA delivery and silencing response in vitro in 6 separate breast cancer cell models (MDA-MB-231, MDA-MB-231-KRas-CRM, MCF-7, AU565, MDA-MB-435 and MDA-MB-468 cells). Using lipopolymers for siRNA complexation and delivery, we found a large variation in siRNA delivery efficiency depending on the specific lipopolymer used for siRNA complexation and delivery. Some lipopolymers were …
Edb-Fn Targeted Peptide–Drug Conjugates For Use Against Prostate Cancer, Shang Eun Park, Kiumars Shamloo, Timothy A. Kristedja, Shaban Darwish, Marco Bisoffi, Keykavous Parang, Rakesh Tiwari
Edb-Fn Targeted Peptide–Drug Conjugates For Use Against Prostate Cancer, Shang Eun Park, Kiumars Shamloo, Timothy A. Kristedja, Shaban Darwish, Marco Bisoffi, Keykavous Parang, Rakesh Tiwari
Pharmacy Faculty Articles and Research
Prostate cancer (PCa) is the most common malignancy in men and is the leading cause of cancer-related male mortality. A disulfide cyclic peptide ligand [CTVRTSADC] 1 has been previously found to target extra domain B of fibronectin (EDB-FN) in the extracellular matrix that can dierentiate aggressive PCa from benign prostatic hyperplasia. We synthesized and optimized the stability of ligand 1 by amide cyclization to obtain [KTVRTSADE] 8 using Fmoc/tBu solid-phase chemistry. Optimized targeting ligand 8 was found to be stable in phosphate buered saline (PBS, pH 6.5, 7.0, and 7.5) and under redox conditions, with a half-life longer than 8 …
Molecular Recognition Of M1-Linked Ubiquitin Chains By Native And Phosphorylated Uban Domains, Lina Herhaus, Henry Van Den Bedem, Sean Teng, Innokentiy Maslennikov, Soichi Wakatsuki, Ivan Dikic, Simin Rahighi
Molecular Recognition Of M1-Linked Ubiquitin Chains By Native And Phosphorylated Uban Domains, Lina Herhaus, Henry Van Den Bedem, Sean Teng, Innokentiy Maslennikov, Soichi Wakatsuki, Ivan Dikic, Simin Rahighi
Pharmacy Faculty Articles and Research
Although the Ub-binding domain in ABIN proteins and NEMO (UBAN) is highly conserved, UBAN-containing proteins exhibit different Ub-binding properties, resulting in their diverse biological roles. Post-translational modifications further control UBAN domain specificity for poly-Ub chains. However, precisely, how the UBAN domain structurally confers such functional diversity remains poorly understood. Here we report crystal structures of ABIN-1 alone and in complex with one or two M1-linked di-Ub chains. ABIN-1 UBAN forms a homo-dimer that provides two symmetrical Ub-binding sites on either side of the coiled-coil structure. Moreover, crystal structures of ABIN1 UBAN in complex with di-Ub chains reveal a concentration-dependency of …
Sensory Primary Cilium Is A Responsive Camp Microdomain In Renal Epithelia, Rinzhin T. Sherpa, Ashraf M. Mohieldin, Rajasekharreddy Pala, Dagmar Wachten, Rennolds S. Ostrom, Surya M. Nauli
Sensory Primary Cilium Is A Responsive Camp Microdomain In Renal Epithelia, Rinzhin T. Sherpa, Ashraf M. Mohieldin, Rajasekharreddy Pala, Dagmar Wachten, Rennolds S. Ostrom, Surya M. Nauli
Pharmacy Faculty Articles and Research
Primary cilia are hair-like cellular extensions that sense microenvironmental signals surrounding cells. The role of adenylyl cyclases in ciliary function has been of interest because the product of adenylyl cyclase activity, cAMP, is relevant to cilia-related diseases. In the present study, we show that vasopressin receptor type-2 (V2R) is localized to cilia in kidney epithelial cells. Pharmacologic inhibition of V2R with tolvaptan increases ciliary length and mechanosensory function. Genetic knockdown of V2R, however, does not have any effect on ciliary length, although the effect of tolvaptan on ciliary length is dampened. Our study reveals that tolvaptan may have a cilia-specific …
Amphiphilic Peptides For Efficient Sirna Delivery, Saghar Mozaffari, Emira Bousoik, Farideh Amirrad, Robert Lamboy, Melissa Coyle, Ryley Hall, Abdulaziz Alasmari, Parvin Mahdipoor, Keykavous Parang, Hamidreza Montazeri Aliabadi
Amphiphilic Peptides For Efficient Sirna Delivery, Saghar Mozaffari, Emira Bousoik, Farideh Amirrad, Robert Lamboy, Melissa Coyle, Ryley Hall, Abdulaziz Alasmari, Parvin Mahdipoor, Keykavous Parang, Hamidreza Montazeri Aliabadi
Pharmacy Faculty Articles and Research
A number of amphiphilic cyclic peptides—[FR]4, [WR]5, and [WK]5—containing hydrophobic and positively-charged amino acids were synthesized by Fmoc/tBu solid-phase peptide methods and evaluated for their efficiency in intracellular delivery of siRNA to triple-negative breast cancer cell lines, MDA-MB-231 and MDA-MB-468, in the presence and absence of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Among the peptides, [WR]5, which contains alternate tryptophan (W) and arginine (R) residues, was found to be the most efficient in the delivery of siRNA by improving the delivery by more than 3-fold when compared to other synthesized cyclic peptides that were not efficient. The data also showed that co-formulation of [WR]5 …
Synthesis And Antiproliferative Activities Of Conjugates Of Paclitaxel And Camptothecin With A Cyclic Cell-Penetrating Peptide, Naglaa Salem El-Sayed, Amir Nasrolahi Shirazi, Muhammad Imran Sajid, Shang Eun Park, Keykavous Parang, Rakesh Tiwari
Synthesis And Antiproliferative Activities Of Conjugates Of Paclitaxel And Camptothecin With A Cyclic Cell-Penetrating Peptide, Naglaa Salem El-Sayed, Amir Nasrolahi Shirazi, Muhammad Imran Sajid, Shang Eun Park, Keykavous Parang, Rakesh Tiwari
Pharmacy Faculty Articles and Research
Cell-penetrating peptide [WR]5 has been previously shown to be an efficient molecular transporter for various hydrophilic and hydrophobic molecules. The peptide was synthesized using Fmoc/tBu solid-phase chemistry, and one arginine was replaced with one lysine to enable the conjugation with the anticancer drugs. Paclitaxel (PTX) was functionalized with an esterification reaction at the C20 hydroxyl group of PTX with glutaric anhydride and conjugated with the cyclic peptide [W(WR)4K(bAla)] in DMF to obtain the peptide-drug conjugate PTX1. Furthermore, camptothecin (CPT) was modified at the C(20)-hydroxyl group through the reaction with triphosgene. Then, it was conjugated with two functionalized cyclic peptides through …
Small Peptide Ligands For Targeting Egfr In Triple Negative Breast Cancer Cells, Hanieh Hossein-Nejad-Ariani, Emad Althagafi, Kamaljit Kaur
Small Peptide Ligands For Targeting Egfr In Triple Negative Breast Cancer Cells, Hanieh Hossein-Nejad-Ariani, Emad Althagafi, Kamaljit Kaur
Pharmacy Faculty Articles and Research
The efficacy of chemotherapy for cancer treatment can be increased by targeted drug delivery to the cancer cells. This is particularly important for triple negative breast cancer (TNBC) for which chemotherapy is a major form of treatment. Here we designed and screened a library of 30 peptides starting with a previously reported epidermal growth factor receptor (EGFR) targeting peptide GE11 (YHWYGYTPQNVI). A direct peptide array-whole cell binding assay, where the peptides are conjugated to a cellulose membrane, was used to identify four peptides with enhanced binding to TNBC cells. Next, the four peptides were synthesized as FITC-labelled soluble peptides to …
Src Family Kinase Inhibitors Block Translation Of Alphavirus Subgenomic Mrnas, Rebecca Broeckel, Sanjay Sarkar, Nicholas A. May, Jennifer Totonchy, Craig N. Kreklywich, Patricia Smith, Lee Graves, Victor R. Defilippis, Mark T. Heise, Thomas E. Morrison, Nathaniel Moorman, Daniel N. Streblow
Src Family Kinase Inhibitors Block Translation Of Alphavirus Subgenomic Mrnas, Rebecca Broeckel, Sanjay Sarkar, Nicholas A. May, Jennifer Totonchy, Craig N. Kreklywich, Patricia Smith, Lee Graves, Victor R. Defilippis, Mark T. Heise, Thomas E. Morrison, Nathaniel Moorman, Daniel N. Streblow
Pharmacy Faculty Articles and Research
Alphaviruses are arthropod-transmitted RNA viruses that can cause arthralgia, myalgia, and encephalitis in humans. Since the role of cellular kinases in alphavirus replication is unknown, we profiled kinetic changes in host kinase abundance and phosphorylation following chikungunya virus (CHIKV) infection of fibroblasts. Based upon the results of this study, we treated CHIKV-infected cells with kinase inhibitors targeting the Src family kinase (SFK)–phosphatidylinositol 3-kinase (PI3K)–AKT–mTORC signaling pathways. Treatment of cells with SFK inhibitors blocked the replication of CHIKV as well as multiple other alphaviruses, including Mayaro virus, O’nyong-nyong virus, Ross River virus, and Venezuelan equine encephalitis virus. Dissecting the effect of …