Membrane Active Antimicrobial Peptides: Translating Mechanistic Insights to Design

Antimicrobial peptides (AMPs) are promising next generation antibiotics that hold great potential for combating bacterial resistance. AMPs can be both bacteriostatic and bactericidal, induce rapid killing and display a lower propensity to develop resistance than do conventional antibiotics. Despite significant progress in the past 30 years, no peptide antibiotic has reached the clinic yet. Poor understanding of the action mechanisms and lack of rational design principles have been the two major obstacles that have slowed progress.

type: 
Journal Paper
journal: 
Frontiers in Neuroscience, Feb 2017, Vol. 11, Article 73, doi: 10.3389/fnins.2017.00073
Url: 
http://journal.frontiersin.org/article/10.3389/fnins.2017.00073/full
Impact Factor: 
3.398
Date of acceptance: 
2017-01-31

Discovery of Rab1 binding sites using an ensemble of clustering methods

Targeting non-native-ligand binding sites for potential investigative and therapeutic applications is an attractive strategy in proteins that share common native ligands, as in Rab1 protein. Rab1 is a subfamily member of Rab proteins, which are members of Ras GTPase superfamily. All Ras GTPase superfamily members bind to native ligands GTP and GDP, that switch on and off the proteins, respectively. Rab1 is physiologically essential for autophagy and transport between endoplasmic reticulum and Golgi apparatus.

type: 
Journal Paper
journal: 
PROTEINS: Structure, Function, and Bioinformatics, doi: 10.1002/prot.25254
Url: 
http://onlinelibrary.wiley.com/doi/10.1002/prot.25254/abstract
Impact Factor: 
2.499
Date of acceptance: 
2017-01-19

Discovery of a novel splice variant of Fcar (CD89) unravels sequence segments necessary for efficient secretion: a story of bad signal peptides and good ones that nevertheless do not make it

The IgA receptor, Fcar (CD89) consists of five sequence segments: two segments (S1, S2) forming the potential signal peptide, two extracellular EC domains that include the IgA binding site, and the transmembrane and cytoplasmic tail (TM/C) region. Numerous Fcar splice variants have been reported with various combinations of the sequence segments mentioned above. Here, we report a novel splice variant termed variant APD isolated from a healthy volunteer that lacks only the IgA-binding EC1 domain.

type: 
Journal Paper
journal: 
Cell Cycle 2016, doi: 10.1080/15384101.2017.1281480
Url: 
http://www.tandfonline.com/doi/full/10.1080/15384101.2017.1281480?scroll=top&needAccess=true
Impact Factor: 
3.952
Date of acceptance: 
2017-01-05

Macrocyclized extended peptides: Inhibiting the substrate-recognition domain of tankyrase

We report a double-click macrocyclization approach for the constraint of peptide inhibitors in non-helical or extended conformations. Our targets are the tankyrase proteins (TNKS), poly(ADP-ribose) polymerases that regulate Wnt signaling by targeting Axin for degradation. TNKS are deregulated in many different cancer types, and inhibition of TNKS therefore represents an attractive therapeutic strategy. However, the clinical development of TNKS-specific PARP inhibitors is challenging due to off-target effects and cellular toxicity.

type: 
Journal Paper
journal: 
Journal of the American Chemical Society, doi: 10.1021/jacs.6b10234
Url: 
http://pubs.acs.org/doi/pdf/10.1021/jacs.6b10234
Impact Factor: 
13.038
Date of acceptance: 
2017-01-12

Toward Understanding the Molecular Recognition of Albumin by p53-Activating Stapled Peptide ATSP-7041

Reactivation of tumor-suppressing activity of p53 protein by targeting its negative regulator MDM2/MDMX has been pursued as a potential anticancer strategy. A promising dual inhibitor of MDM2/MDMX that has been developed and is currently in clinical trials is the stapled peptide ATSP-7041. The activity of this molecule is reported to be modulated in the presence of serum. Albumin is the most abundant protein in serum and is known to bind reversibly to several molecules. To study this interaction, we develop a protocol combining molecular modeling, docking, and simulations.

type: 
Journal Paper
journal: 
The Journal of Physical Chemistry B, 2017, 121 (4), pg 657-670, doi : 10.1021/acs.jpcb.6b09900
Url: 
http://pubs.acs.org/doi/abs/10.1021/acs.jpcb.6b09900
Impact Factor: 
2.883

Genome-wide analysis of mRNAs associated with mouse peroxisomes

Background: RNA is often targeted to be localized to the specific subcellular compartments. Specific localization of mRNA is believed to be an important mechanism for targeting their protein products to the locations, where their function is required.

type: 
Journal Paper
journal: 
BMC Genomics 2016, 17 (Supp 13), 1028, doi: 10.1186/s12864-016-3330-x
Url: 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259856/
Impact Factor: 
3.869

Structural analyses of 2015-updated drugresistant mutations in HIV-1 protease: an implication of protease inhibitor crossresistance

Background: Strategies to control HIV for improving the quality of patient lives have been aided by the Highly Active Anti-Retroviral Therapy (HAART), which consists of a cocktail of inhibitors targeting key viral enzymes. Numerous new drugs have been developed over the past few decades but viral resistances to these drugs in the targeted viral enzymes are increasingly reported. Nonetheless the acquired mutations often reduce viral fitness and infectivity.

type: 
Journal Paper
journal: 
BMC Bioinformatics 2016, 17(Suppl 19):500 doi: 10.1186/s12859-016-1372-3
Url: 
https://bmcbioinformatics.biomedcentral.com/articles/10.1186/s12859-016-1372-3
Impact Factor: 
2.435

Fusion of Magnetic and Visual Sensors for Indoor Localization: Infrastructure-free and More Effective

Accurate and infrastructure-free indoor positioning can be very useful in a variety of applications. However, most

type: 
Journal Paper
journal: 
IEEE Transactions on Medical Imaging, Issue 99, 2016, doi: 10.1109/TMI.2016.2623357
Impact Factor: 
3.756

Automated Classification for Pathological Prostate Images using AdaBoost-based

We present an AdaBoost-based Ensemble Learning for supporting automated Gleason grading of prostate adenocarcinoma (PRCA). The method is able to differentiate Gleason patterns 4–5 from patterns 1–3 as the patterns 4-5 are correlated to more aggressive disease while patterns 1-3 tend to reflect more favorable patient outcome. This method is based on various feature descriptors and classifiers for multiple color channels, including color channels of red, green and blue, as well as the optical intensity of hematoxylin and eosin stainings.

type: 
Conference Paper/Poster
journal: 
2016 IEEE Sympsosium Series on Computational Intelligence (IEEE SSCI 2016) Dec 6 to 9, Athens, Greece,

Development of Cell-Permeable, Non-Helical, Constrained Peptides to Target a Key Protein-Protein Interaction in Ovarian Cancer

There is a lack of current treatment options for ovarian clear cell carcinoma (CCC) and the cancer is often resistant to platinum-based chemotherapy. Hence there is an urgent need for novel therapeutics. The transcription factor hepatocyte nuclear factor 1β (HNF1β) is ubiquitously overexpressed in CCC and is seen as an attractive therapeutic target. This was validated through shRNA-mediated knockdown of the target protein, HNF1β, in five high- and low-HNF1β-expressing CCC lines.

type: 
Journal Paper
journal: 
Angewandte Chemie, Vol. 56, Issue 2, Jan 9, 2017 Pg 524-529, doi: 10.1002/anie.201609427
pubmed: 
27918136
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/27918136
Impact Factor: 
11.709
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