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Articles 1 - 8 of 8
Full-Text Articles in Medicine and Health Sciences
A Computational Model Reveals The Action Of Gβγ At An Inter-Subunit Cleft To Activate Girk1 Channels, Rahul Mahajan, Junghoon Ha, Miao Zhang, Takeharu Kawano, Tohru Kozasa, Diomedes E. Logothetis
A Computational Model Reveals The Action Of Gβγ At An Inter-Subunit Cleft To Activate Girk1 Channels, Rahul Mahajan, Junghoon Ha, Miao Zhang, Takeharu Kawano, Tohru Kozasa, Diomedes E. Logothetis
Pharmacy Faculty Articles and Research
The atrial G protein-regulated inwardly rectifying K+ (GIRK1 and GIRK4) heterotetrameric channels underlie the acetylcholine-induced K+ current responsible for vagal inhibition of heart rate and are activated by the G protein βγ subunits (Gβγ). We used a multistage protein-protein docking approach with data from published structures of GIRK1 and Gβγ to generate an experimentally testable interaction model of Gβγ docked onto the cytosolic domains of the GIRK1 homotetramer. The model suggested a mechanism by which Gβγ promotes the open state of a specific cytosolic gate in the channel, the G-loop gate. The predicted structure showed that the Gβ subunit interacts …
Tigecycline Induction Of Phenol-Soluble Modulins By Invasive Methicillin-Resistant Staphylococcus Aureus Strains, Jason Yamaki, Timothy Synold, Annie Wong-Beringer
Tigecycline Induction Of Phenol-Soluble Modulins By Invasive Methicillin-Resistant Staphylococcus Aureus Strains, Jason Yamaki, Timothy Synold, Annie Wong-Beringer
Pharmacy Faculty Articles and Research
We examined the effects of tigecycline on three types of exoproteins, α-type phenol-soluble modulins (PSMα1 to PSMα4), α-hemolysin, and protein A, in 13 methicillin-resistant Staphylococcus aureus isolates compared to those of clindamycin and linezolid. Paradoxical increases in PSMαs occurred in 77% of the isolates with tigecycline at 1/4 and 1/8 MICs and clindamycin at 1/8 MIC compared to only 23% of the isolates with linezolid at 1/8 MIC. Induction was specific to PSMα1 to PSMα4, as protein A and α-hemolysin production was decreased under the same conditions by all of the antibiotics used.
Cyclic Peptides Containing Tryptophan And Arginine As Src Kinase Inhibitors, Amir Nasrolahi Shirazi, Rakesh Tiwari, Alex Brown, Dindyal Mandal, Gongqin Sun, Keykavous Parang
Cyclic Peptides Containing Tryptophan And Arginine As Src Kinase Inhibitors, Amir Nasrolahi Shirazi, Rakesh Tiwari, Alex Brown, Dindyal Mandal, Gongqin Sun, Keykavous Parang
Pharmacy Faculty Articles and Research
A number of cyclic and linear peptides containing various combinations of amino acids were evaluated for their Src kinase inhibitory potency. Among all the peptides, cyclic decapeptide C[RW]5 containing alternative arginine (R) and tryptophan (W) residues was found to be the most potent Src kinase inhibitor. C[RW]5 showed higher inhibitory activity (IC50=2.8 μM) than C[KW]5, L(KW)5, C[RW]4, and C[RW]3 with IC50 values of 46.9, 69.1, 21.5, and 25.0 μM, respectively, as determined in a fluorescence intensity-based assay. Thus, the cyclic nature, the presence of arginine, ring size, and the number of amino acids in the structure of the peptide were …
Design, Synthesis And Evaluation Of Antimicrobial Activity Of N-Terminal Modified Leucocin A Analogues, Krishna Chaitanya Bodapati, Rania Soudy, Hashem Etayash, Michael Stiles, Kamaljit Kaur
Design, Synthesis And Evaluation Of Antimicrobial Activity Of N-Terminal Modified Leucocin A Analogues, Krishna Chaitanya Bodapati, Rania Soudy, Hashem Etayash, Michael Stiles, Kamaljit Kaur
Pharmacy Faculty Articles and Research
Class IIa bacteriocins are potent antimicrobial peptides produced by lactic acid bacteria to destroy competing microorganisms. The N-terminal domain of these peptides consists of a conserved YGNGV sequence and a disulphide bond. The YGNGV motif is essential for activity, whereas, the two cysteines involved in the disulphide bond can be replaced with hydrophobic residues. The C-terminal region has variable sequences, and folds into a conserved amphipathic α-helical structure. To elucidate the structure–activity relationship in the N-terminal domain of these peptides, three analogues (1–3) of a class IIa bacteriocin, Leucocin A (LeuA), were designed and synthesized by …
Revisiting The Fundamentals In The Design And Control Of Nanoparticulate Colloids In The Frame Of Soft Chemistry, Vuk Uskoković
Revisiting The Fundamentals In The Design And Control Of Nanoparticulate Colloids In The Frame Of Soft Chemistry, Vuk Uskoković
Pharmacy Faculty Articles and Research
This review presents thoughts on some of the fundamental features of conceptual models applied in the design of fine particles in the frames of colloid and soft chemistry. A special emphasis is placed on the limitations of these models, an acknowledgment of which is vital in improving their intricacy and effectiveness in predicting the outcomes of the corresponding experimental settings. Thermodynamics of self-assembly phenomena illustrated on the examples of protein assembly and micellization is analyzed in relation to the previously elaborated thesis that each self-assembly in reality presents a co-assembly, since it implies a mutual reorganization of the assembling system …
Chikungunya Virus Infection Results In Higher And Persistent Viral Replication In Aged Rhesus Macaques Due To Defects In Anti-Viral Immunity, Ilhem Messaoudi, Jennifer Totonchy, Thomas Totonchy, Craig N. Kreklywich, Kristen Haberthur, Laura Springgay, James D. Brien, Michael S. Diamond, Victor R. Defilippis, Daniel N. Streblow
Chikungunya Virus Infection Results In Higher And Persistent Viral Replication In Aged Rhesus Macaques Due To Defects In Anti-Viral Immunity, Ilhem Messaoudi, Jennifer Totonchy, Thomas Totonchy, Craig N. Kreklywich, Kristen Haberthur, Laura Springgay, James D. Brien, Michael S. Diamond, Victor R. Defilippis, Daniel N. Streblow
Pharmacy Faculty Articles and Research
Chikungunya virus (CHIKV) is a re-emerging mosquito-borne Alphavirus that causes a clinical disease involving fever, myalgia, nausea and rash. The distinguishing feature of CHIKV infection is the severe debilitating poly-arthralgia that may persist for several months after viral clearance. Since its re-emergence in 2004, CHIKV has spread from the Indian Ocean region to new locations including metropolitan Europe, Japan, and even the United States. The risk of importing CHIKV to new areas of the world is increasing due to high levels of viremia in infected individuals as well as the recent adaptation of the virus to the mosquito species Aedes …
Aberrant Proliferation In Cxcr7+ Endothelial Cells Via Degradation Of The Retinoblastoma Protein, Jennifer Totonchy, Jessica M. Osborn, Sara Botto, Lisa Clepper, Ashlee V. Moses
Aberrant Proliferation In Cxcr7+ Endothelial Cells Via Degradation Of The Retinoblastoma Protein, Jennifer Totonchy, Jessica M. Osborn, Sara Botto, Lisa Clepper, Ashlee V. Moses
Pharmacy Faculty Articles and Research
Angiogenesis is a critical factor in the growth and dissemination of solid tumors. Indeed, tumor vasculature is abnormal and contributes to the development and spread of malignancies by creating a hostile microenvironment. The alternative SDF-1/CXCL12 receptor, CXCR7, is frequently and specifically expressed in tumor-associated vessels. In this study, we examine the role of endothelium-expressed CXCR7 in tumor vascular dysfunction by specifically examining the contribution of CXCR7 to endothelial cell (EC) proliferation. We demonstrate that CXCR7 expression is sufficient to drive post-confluent growth in EC cultures. Further, we provide a novel mechanism for CXCR7-mediated proliferation via proteasomal degradation of the tumor …
Self-Assembled Surfactant Cyclic Peptide Nanostructures As Stabilizing Agents, Dindyal Mandal, Rakesh Tiwari, Amir Nasrolahi Shirazi, Donghoon Oh, Guofeng Ye, Antara Banerjee, Arpita Yadav, Keykavous Parang
Self-Assembled Surfactant Cyclic Peptide Nanostructures As Stabilizing Agents, Dindyal Mandal, Rakesh Tiwari, Amir Nasrolahi Shirazi, Donghoon Oh, Guofeng Ye, Antara Banerjee, Arpita Yadav, Keykavous Parang
Pharmacy Faculty Articles and Research
A number of cyclic peptides including [FR](4), [FK](4), [WK](5), [CR](4), [AK](4), and [WR](n) (n = 3-5) containing L-amino acids were produced using solid-phase peptide synthesis. We hypothesized that an optimal balance of hydrophobicity and charge could generate self-assembled nanostructures in aqueous solution by intramolecular and/or intermolecular interactions. Among all the designed peptides, [WR](n) (n = 3-5) generated self-assembled vesicle-like nanostructures at room temperature as shown by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and/or dynamic light scattering (DLS). This class of peptides represents the first report of surfactant-like cyclic peptides that self-assemble into nanostructures. A plausible mechanistic insight into …