Medicinal-Pharmaceutical Chemistry Commons^™

Cyclic Peptide-Gadolinium Nanocomplexes As Sirna Delivery Tools, Amir Nasrolahi Shirazi, Muhammad Imran Sajid, Dindyal Mandal, David Stickley, Stephanie Nagasawa, Joshua Long, Sandeep Lohan, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

We have recently reported that a cyclic peptide containing five tryptophan, five arginine, and one cysteine amino acids [(WR)₅C], was able to produce peptide-capped gadolinium nanoparticles, [(WR)₅C]-GdNPs, in the range of 240 to 260 nm upon mixing with an aqueous solution of GdCl₃. Herein, we report [(WR)₅C]-GdNPs as an efficient siRNA delivery system. The peptide-based gadolinium nanoparticles (50 µM) did not exhibit significant cytotoxicity (~93% cell viability at 50 µM) in human leukemia T lymphoblast cells (CCRF-CEM) and triple-negative breast cancer cells (MDA-MB-231) after 48 h. Fluorescence-activated cell sorting (FACS) analysis indicated …

Atomistic Simulations And In Silico Mutational Profiling Of Protein Stability And Binding In The Sars-Cov-2 Spike Protein Complexes With Nanobodies: Molecular Determinants Of Mutational Escape Mechanisms, Gennady M. Verkhivker, Steve Agajanian, Deniz Yasar Oztas, Grace Gupta

Mathematics, Physics, and Computer Science Faculty Articles and Research

Structure-functional studies have recently revealed a spectrum of diverse high-affinity nanobodies with efficient neutralizing capacity against SARS-CoV-2 virus and resilience against mutational escape. In this study, we combine atomistic simulations with the ensemble-based mutational profiling of binding for the SARS-CoV-2 S-RBD complexes with a wide range of nanobodies to identify dynamic and binding affinity fingerprints and characterize the energetic determinants of nanobody-escaping mutations. Using an in silico mutational profiling approach for probing the protein stability and binding, we examine dynamics and energetics of the SARS-CoV-2 complexes with single nanobodies Nb6 and Nb20, VHH E, a pair combination VHH E + …

Theranostic Applications Of Sirna Bioconjugates In Cancer Detection And Treatment, Sunil S. Shah

Seton Hall University Dissertations and Theses (ETDs)

Abstract

The emerging field of RNA nanotechnology has led to rapid advances in the applications of RNA in chemical biology, medicinal chemistry, and biotechnology. At the forefront of its utility is the ability to self-assemble multiple siRNAs into nanostructure formulations capable of targeting selected oncogenes and potentiating the gene therapy of malignant tumors. Self-assembled siRNA integrates multiple siRNAs within a single molecular platform for silencing multiple oncogenic mRNA targets with high precision and efficacy to potentially induce cancer cell apoptosis through the RNA interference (RNAi) pathway. Furthermore, the conjugation of siRNA self-assemblies with bio-active probes results in multi-functional theranostic (therapy+diagnostic) …

Reeling In New Antibiotics: Synthesis And Antimicrobial Susceptibility Testing Of Zinc-Binding Clavanins From Styela Clava (Sea Squirt), Eduardo Badillo-Colberg

Honors Scholar Theses

Clavanins have been a quite rarely studied antimicrobial peptide (AMP) family. Though the data in the few studies published on the matter and in theoretical experimental data presented by the Wang lab in their peptide library creation [14], in that the members of this family could potentially be quite effective novel antimicrobial candidates. Among those that have been targets of studies, Clavanin A has been at the forefront of this endeavor of finding effective novel antimicrobial peptides[14]. In these aforementioned studies, Clavanin A has been shown to be quite effective against many different bacterial strains, which begs the question as …

The Mechanism Of Β-N-Methylamino-L-Alanine Inhibition Of Trna Aminoacylation And Its Impact On Misincorporation, Nien-Ching Han, Tammy J. Bullwinkle, Kaeli F. Loeb, Kym F. Faull, Kyle Mohler, Jesse Rinehart, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

β-N-methylamino-l-alanine (BMAA) is a nonproteinogenic amino acid that has been associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). BMAA has been found in human protein extracts; however, the mechanism by which it enters the proteome is still unclear. It has been suggested that BMAA is misincorporated at serine codons during protein synthesis, but direct evidence of its cotranslational incorporation is currently lacking. Here, using LC-MS–purified BMAA and several biochemical assays, we sought to determine whether any aminoacyl-tRNA synthetase (aaRS) utilizes BMAA as a substrate for aminoacylation. Despite BMAA's previously predicted misincorporation at serine …