Incorporation of Putative Helix-Breaking Amino Acids in the Design of Novel Stapled Peptides: Exploring Biophysical and Cellular Permeability Properties

Published date : 20 Jun 2019

Stapled α-helical peptides represent an emerging superclass of macrocyclic molecules with drug-like properties, including high-affinity target binding, protease resistance, and membrane permeability. As a model system for probing the chemical space available for optimizing these properties, we focused on dual Mdm2/MdmX antagonist stapled peptides related to the p53 N-terminus. Specifically, we first generated a library of ATSP-7041 (Chang et al., 2013) analogs iteratively modified by L-Ala and D-amino acids.

type
Journal Paper
journal
Molecules 2019, Vol. 24, Issue 12, 2292; https://doi.org/10.3390/molecules24122292
Impact Factor
3.060

Chemogenomic profiling in yeast reveals antifungal mode-of-action of polyene macrolactam auroramycin

Published date : 10 Jun 2019

In this study, we report antifungal activity of auroramycin against Candida albicans, Candida tropicalis, and Cryptococcus neoformans. Auroramycin, a potent antimicrobial doubly glycosylated 24-membered polyene macrolactam, was previously isolated and characterized, following CRISPR-Cas9 mediated activation of a silent polyketide synthase biosynthetic gene cluster in Streptomyces rosesporous NRRL 15998. Chemogenomic profiling of auroramycin in yeast has linked its antifungal bioactivity to vacuolar transport and membrane organization.

type
Journal Paper
journal
PLOS ONE, 10 June 2019, doi: 10.1371/journal.pone.0218189
Impact Factor
2.766

The APD Skin Monitoring App for wound monitoring: Image processing, area plot, and colour histogram

Published date : 30 May 2019

Being often irregular in shape, accurate measurements of wounds are often challenging. Tracing or length measurement by the longest dimension are often inaccurate and time-consuming to carry out. Yet, proper wound area monitoring is essential for wound care. Instead of multiple clinical visits, which also increase the burden on health care systems and the associated expenses, patients can take the responsibility for their own wound progress.

type
Journal Paper
journal
Scientific Phone Apps and Mobile Devices (2019) 5:3, doi: 10.30943/2019/2805019

Preclinical Characteristics of the Irreversible Pan-HER Kinase Inhibitor Neratinib Compared with Lapatinib: Implications for the Treatment of HER2-Positive and HER2-Mutated Breast Cancer

Published date : 28 May 2019

An estimated 15–20% of breast cancers overexpress human epidermal growth factor receptor 2 (HER2/ERBB2/neu). Two small-molecule tyrosine kinase inhibitors (TKIs), lapatinib and neratinib, have been approved for the treatment of HER2-positive (HER2+) breast cancer.

type
Journal Paper
journal
Cancers 2019, Vol. 11, Issue 6, 37, doi: 10.3390/cancers11060737
Impact Factor
5.326

Genomics-driven discovery of a biosynthetic gene cluster required for the synthesis of BII-Rafflesfungin from the fungus Phoma sp. F3723

Published date : 23 May 2019

BACKGROUND:
Phomafungin is a recently reported broad spectrum antifungal compound but its biosynthetic pathway is unknown. We combed publicly available Phoma genomes but failed to find any putative biosynthetic gene cluster that could account for its biosynthesis.

type
Journal Paper
journal
BMC Genomics 2019, 20:374, doi: 10.1186/s12864-019-5762-6
Impact Factor
3.730

Exploring Gatekeeper Mutations in EGFR through Computer Simulations

Published date : 17 May 2019

The emergence of resistance against drugs that inhibit a particular protein is a major problem in targeted therapy. There is a clear need for rigorous methods to predict the likelihood of specific drug-resistance mutations arising in response to the binding of a drug. In this work we attempt to develop a robust computational protocol for predicting drug resistant mutations at the gatekeeper position (T790) in EGFR. We explore how mutations at this site affects interactions with ATP and three drugs that are currently used in clinics. We found, as expected,

type
Journal Paper
journal
Journal of Chemical Information and Modeling, 2019, doi: 10.1021/acs.jcim.9b00361
Impact Factor
3.804

AppA: a web server for analysis, comparison, and visualization of contact residues and interfacial waters of antibody–antigen structures and models

Published date : 09 May 2019

The study of contact residues and interfacial waters of antibody–antigen (Ab-Ag) structures could help in understanding the principles of antibody–antigen interactions as well as provide guidance for designing antibodies with improved affinities. Given the rapid pace with which new antibody–antigen structures are deposited in the protein databank (PDB), it is crucial to have computational tools to analyze contact residues and interfacial waters, and investigate them at different levels.

type
Journal Paper
journal
Nuclei Acids Research, 2019, doi: 10.1093/nar/gkz358
Impact Factor
11.561

A novel method for the capture-based purification of whole viral native RNA genomes

Published date : 08 May 2019

Current technologies for targeted characterization and manipulation of viral RNA primarily involve amplification or ultracentrifugation with isopycnic gradients of viral particles to decrease host RNA background. The former strategy is non-compatible for characterizing properties innate to RNA strands such as secondary structure, RNA-RNA interactions, and also for nanopore direct RNA sequencing involving the sequencing of native RNA strands. The latter strategy, ultracentrifugation, causes loss in genomic information due to its inability to retrieve unassembled viral RNA.

type
Journal
journal
AMB Express, 2019 Apr 8;9(1):45. doi: 10.1186/s13568-019-0772-y
Impact Factor
1.719

Chemical-genetic interaction landscape of mono-(2-ethylhexyl)-phthalate using chemogenomic profiling in yeast

Published date : 15 Apr 2019

Integration of chemical-genetic interaction data with biological functions provides a mechanistic understanding of how toxic compounds affect cells. Mono-(2-ethylhexyl)-phthalate (MEHP) is an active metabolite of di-(2-ethylhexyl)-phthalate (DEHP), a commonly used plasticizer. MEHP adversely affects human health causing hepatotoxicity and reproductive toxicity. How MEHP affects cellular physiology is not fully understood. We utilized a genome-wide competitive fitness-based assay called 'chemogenomic profiling' to determine the genetic interaction map of MEHP in Saccharomyces cerevisiae.

type
Journal Paper
journal
Chemosphere, Vol. 228, 2019, Pg 219-231, doi: 10.1016/j.chemosphere.2019.04.100
Impact Factor
4.427

Role of the IgE variable heavy chain in FcεRIa and superantigen binding in allergy and immunotherapy

Published date : 14 Apr 2019

Background
Variable heavy chain (VH) family frameworks (FWRs) have been reported to affect antibody receptor and superantigen binding; however, such effects in IgE remain largely unknown. Given that VH family biases have been previously reported in IgE of certain allergies, there is a need to investigate this phenomenon for biotechnological and therapeutic purposes.

type
Journal Paper
journal
Journal of Allergy and Clinical Immunology, April 2019, doi : 10.1016/j.jaci.2019.03.028
Impact Factor
13.258