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Amino Acids, Peptides, and Proteins Commons™

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Pharmacy Faculty Articles and Research

Series

2015

Articles 1 - 9 of 9

Full-Text Articles in Amino Acids, Peptides, and Proteins

Cysteine And Arginine-Rich Peptides As Molecular Carriers, Amir Nasrolahi Shirazi, Naglaa Salem El-Sayed, Dindayal Mandal, Rakesh Tiwari, Kathy Tavakoli, Matthew Eteshem, Keykavous Parang Nov 2015

Cysteine And Arginine-Rich Peptides As Molecular Carriers, Amir Nasrolahi Shirazi, Naglaa Salem El-Sayed, Dindayal Mandal, Rakesh Tiwari, Kathy Tavakoli, Matthew Eteshem, Keykavous Parang

Pharmacy Faculty Articles and Research

A number of linear and cyclic peptides containing alternative arginine and cysteine residues, namely linear (CR)3, linear (CR)4, linear (CR)5, cyclic [CR]4, and cyclic [CR]5, were synthesized. The peptides were evaluated for their ability to deliver two molecular cargos, fluorescence-labeled cell-impermeable negatively charged phosphopeptide (F′-GpYEEI) and fluorescence-labeled lamivudine (F′-3TC), intracellularly in human leukemia cancer (CCRF-CEM) cells. We investigated the role of cyclization and the number of amino acids in improving the transporting ability of the peptides. The flow cytometry studies suggested that the synthesized peptides were able to work efficiently as …

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Real-Time Detection Of Breast Cancer Cells Using Peptidefunctionalized Microcantilever Arrays, Hashem Etayash, Keren Jiang, Sarfuddin Azmi, Thomas Thundat, Kamaljit Kaur Oct 2015

Real-Time Detection Of Breast Cancer Cells Using Peptidefunctionalized Microcantilever Arrays, Hashem Etayash, Keren Jiang, Sarfuddin Azmi, Thomas Thundat, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Ligand-directed targeting and capturing of cancer cells is a new approach for detecting circulating tumor cells (CTCs). Ligands such as antibodies have been successfully used for capturing cancer cells and an antibody based system (CellSearch®) is currently used clinically to enumerate CTCs. Here we report the use of a peptide moiety in conjunction with a microcantilever array system to selectively detect CTCs resulting from cancer, specifically breast cancer. A sensing microcantilever, functionalized with a breast cancer specific peptide 18-4 (WxEAAYQrFL), showed significant deflection on cancer cell (MCF7 and MDA-MB-231) binding compared to when exposed to noncancerous (MCF10A and HUVEC) cells. …

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Electrochemical Characterization Of Protein Adsorption Onto Yngrt-Au And Vlgxe-Au Surfaces, Hanna Trzeciakiewicz, Jose Esteves-Villanueva, Rania Soudy, Kamaljit Kaur, Sanela Martic-Milne Aug 2015

Electrochemical Characterization Of Protein Adsorption Onto Yngrt-Au And Vlgxe-Au Surfaces, Hanna Trzeciakiewicz, Jose Esteves-Villanueva, Rania Soudy, Kamaljit Kaur, Sanela Martic-Milne

Pharmacy Faculty Articles and Research

The adsorption of the proteins CD13, mucin and bovine serum albumin on VLGXE-Au and YNGRT-Au interfaces was monitored by electrochemical impedance spectroscopy in the presence of [Fe(CN)6]3−/4−. The hydrophobicity of the Au surface was tailored using specific peptides, blocking agents and diluents. The combination of blocking agents (ethanolamine or n-butylamine) and diluents (hexanethiol or 2-mercaptoethanol) was used to prepare various peptide-modified Au surfaces. Protein adsorption onto the peptide-Au surfaces modified with the combination of n-butylamine and hexanethiol produced a dramatic decrease in the charge transfer resistance, Rct, for all three proteins. In contrast, polar peptide-surfaces induced a minimal change in …

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Molecular Overlap In The Regulation Of Sk Channels By Small Molecules And Phosphoinositides, Miao Zhang, Xuan-Yu Meng, Ji-Fang Zhang, Meng Cui, Diomedes E. Logothetis Jul 2015

Molecular Overlap In The Regulation Of Sk Channels By Small Molecules And Phosphoinositides, Miao Zhang, Xuan-Yu Meng, Ji-Fang Zhang, Meng Cui, Diomedes E. Logothetis

Pharmacy Faculty Articles and Research

Phosphatidylinositol 4,5-bisphosphate (PIP2) directly interacts with the small-conductance Ca2+-activated K+ 2-a (SK2-a) channel/calmodulin complex, serving as a critical element in the regulation of channel activity. We report that changes of protein conformation in close proximity to the PIP2 binding site induced by a small-molecule SK channel modulator, NS309, can effectively enhance the interaction between the protein and PIP2 to potentiate channel activity. This novel modulation of PIP2 sensitivity by small-molecule drugs is likely not to be limited in its application to SK channels, representing an intriguing strategy to develop drugs controlling the activity of the large number of PIP2-dependent proteins.

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Cationic Cell-Penetrating Peptides Are Potent Furin Inhibitors, Bruno Ramos-Molina, Adam N. Lick, Amir Nasrolahi Shirazi, Donghoon Oh, Rakesh Tiwari, Naglaa Salem El-Sayed, Keykavous Parang, Iris Lindberg Jun 2015

Cationic Cell-Penetrating Peptides Are Potent Furin Inhibitors, Bruno Ramos-Molina, Adam N. Lick, Amir Nasrolahi Shirazi, Donghoon Oh, Rakesh Tiwari, Naglaa Salem El-Sayed, Keykavous Parang, Iris Lindberg

Pharmacy Faculty Articles and Research

Cationic cell-penetrating peptides have been widely used to enhance the intracellular delivery of various types of cargoes, such as drugs and proteins. These reagents are chemically similar to the multi-basic peptides that are known to be potent proprotein convertase inhibitors. Here, we report that both HIV-1 TAT47-57 peptide and the Chariot reagent are micromolar inhibitors of furin activity in vitro. In agreement, HIV-1 TAT47-57 reduced HT1080 cell migration, thought to be mediated by proprotein convertases, by 25%. In addition, cyclic polyarginine peptides containing hydrophobic moieties which have been previously used as transfection reagents also exhibited potent furin inhibition in vitro …

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Synthesis And Characterization Of A New Peptide Prodrug Of Glucosamine With Enhanced Gut Permeability, Hamed Gilzad Kohan, Kamaljit Kaur, Fakhreddin Jamali May 2015

Synthesis And Characterization Of A New Peptide Prodrug Of Glucosamine With Enhanced Gut Permeability, Hamed Gilzad Kohan, Kamaljit Kaur, Fakhreddin Jamali

Pharmacy Faculty Articles and Research

The aim of this study was to synthesize a peptide prodrug of glucosamine (GlcN) with increased gut permeability through the gut peptide transporter 1 (PepT1). Glycine-Valine ester derivative of GlcN (GVG) was synthesised using solid phase synthesis followed by characterization and evaluation of its physicochemical and intestinal stability. In addition, GVG was evaluated for its ability to be biotransformed to GlcN in the liver homogenate. In vitro absorption of the new prodrug through everted rat gut was also assessed. GVG demonstrated significant and meaningful increased gut permeability as compared with GlcN. It showed favorable stability in the gut and a …

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Targeting Cell Cycle Proteins In Breast Cancer Cells With Sirna By Using Lipid-Substituted Polyethylenimines, Manoj Parmar, Hamidreza Montazeri Aliabadi, Parvin Mahdipoor, Cezary Kucharski, Robert Maranchuk, Judith C. Hugh, Hasan Uludag Jan 2015

Targeting Cell Cycle Proteins In Breast Cancer Cells With Sirna By Using Lipid-Substituted Polyethylenimines, Manoj Parmar, Hamidreza Montazeri Aliabadi, Parvin Mahdipoor, Cezary Kucharski, Robert Maranchuk, Judith C. Hugh, Hasan Uludag

Pharmacy Faculty Articles and Research

The cell cycle proteins are key regulators of cell cycle progression whose de-regulation is one of the causes of breast cancer. RNA interference (RNAi) is an endogenous mechanism to regulate gene expression and it could serve as the basis of regulating aberrant proteins including cell cycle proteins. Since the delivery of small interfering RNA (siRNA) is a main barrier for implementation of RNAi therapy, we explored the potential of a non-viral delivery system, 2.0 kDa polyethylenimines substituted with linoleic acid and caprylic acid, for this purpose. Using a library of siRNAs against cell cycle proteins, we identified cell division cycle …

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Design, Synthesis, Antiviral Activity, And Pre-Formulation Development Of Poly-Larginine- Fatty Acyl Derivatives Of Nucleoside Reverse Transcriptase Inhibitors, Bhanu P. Pemmaraju, Swapnil Malekar, Hitesh K. Agarwal, Rakesh Tiwari, Donghoon Oh, Gustavo F. Doncel, David R. Worthen, Keykavous Parang Jan 2015

Design, Synthesis, Antiviral Activity, And Pre-Formulation Development Of Poly-Larginine- Fatty Acyl Derivatives Of Nucleoside Reverse Transcriptase Inhibitors, Bhanu P. Pemmaraju, Swapnil Malekar, Hitesh K. Agarwal, Rakesh Tiwari, Donghoon Oh, Gustavo F. Doncel, David R. Worthen, Keykavous Parang

Pharmacy Faculty Articles and Research

The objective of this work was to design conjugates of anti-HIV nucleosides conjugated with fatty acids and cell-penetrating poly-L-arginine (polyArg) peptides. Three conjugates of polyArg cell-penetrating peptides with fatty acyl derivatives of alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC) were synthesized. In general, the compounds exhibited anti-HIV activity against X4 and R5 cell-free virus with EC50 values of 1.5–16.6 μM. FLT-CO-(CH2)12-CO-(Arg)7 exhibited EC50 values of 2.9 μM and 3.1 μM against X4 and R5 cell-free virus, respectively. The FLT conjugate was selected for further preformulation studies by determination of solution state degradation and lipid solubility. The compound was found to …

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Kaposi Sarcoma Herpesvirus Induces Ho-1 During De Novo Infection Of Endothelial Cells Via Viral Mirna-Dependent And -Independent Mechanisms, Sara Botto, Jennifer Totonchy, Jean K. Gustin, Ashlee V. Moses Jan 2015

Kaposi Sarcoma Herpesvirus Induces Ho-1 During De Novo Infection Of Endothelial Cells Via Viral Mirna-Dependent And -Independent Mechanisms, Sara Botto, Jennifer Totonchy, Jean K. Gustin, Ashlee V. Moses

Pharmacy Faculty Articles and Research

Kaposi sarcoma (KS) herpesvirus (KSHV) infection of endothelial cells (EC) is associated with strong induction of heme oxygenase-1 (HO-1), a stress-inducible host gene that encodes the rate-limiting enzyme responsible for heme catabolism. KS is an angioproliferative tumor characterized by the proliferation of KSHV-infected spindle cells, and HO-1 is highly expressed in such cells. HO-1 converts the pro-oxidant, proinflammatory heme molecule into metabolites with antioxidant, antiinflammatory, and proliferative activities. Previously published work has shown that KSHV-infected EC in vitro proliferate in response to free heme in a HO-1-dependent manner, thus implicating virus-enhanced HO-1 activity in KS tumorigenesis. The present study investigated …

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