ABSTRACT
Antimicrobial drug discovery has slowed considerably over the last few decades. One major cause for concern is the lack of innovative approaches to treat infections caused by mycobacteria such as TB. Herein we demonstrate that our Small Molecule Variable Ligand Display (SMLVD) method for nanoparticle antibiotic discovery can be expanded around a ligand feed ratio parameter space to identify gold nanoparticle conjugates that are potent inhibitors of mycobacteria growth, with our most potent inhibitor able to reduce growth by five orders of magnitude at 8 µM.
Subject(s)
Gold/chemistry , Metal Nanoparticles/chemistry , Sulfhydryl Compounds/chemistry , Cell Line , Cell Survival/drug effects , Erythrocytes/cytology , Erythrocytes/drug effects , Hemolysis/drug effects , Humans , Metal Nanoparticles/toxicity , Microbial Sensitivity Tests , Mycobacterium smegmatis/drug effectsABSTRACT
The ability of oligonucleotides to mediate the formation of inorganic materials is now well established. RNA and DNA are proving to be capable of mediating the formation of inorganic nanoparticles with sequence-specific control over nanoparticle size, shape, and even atomic-level crystallinity. Here we describe methods for isolating specific RNA sequences from large random sequence libraries that either bind to precut inorganic crystal wafers with high affinity or influence inorganic crystal growth.
Subject(s)
Inorganic Chemicals/chemistry , RNA/chemistry , RNA/genetics , SELEX Aptamer Technique/methods , Base Sequence , DNA-Directed RNA Polymerases/metabolism , Metal Nanoparticles/chemistry , Platinum/chemistry , Polymerase Chain Reaction , Promoter Regions, Genetic/genetics , Surface Properties , Transcription, Genetic , Viral Proteins/metabolismABSTRACT
The ability of peptides selected via phage display to mediate the formation of inorganic nanoparticles is now well established. The atomic-level interactions between the selected peptides and the metal ion precursors are in most instances, however, largely obscure. We identified a new peptide sequence that is capable of mediating the formation of Ag nanoparticles. Surprisingly, nanoparticle formation requires the presence of peptide, HEPES buffer, and light; the absence of any one of these compromises nanoparticle formation. Electrochemical experiments revealed that the peptide binds Ag+ in a 3 Ag+:1 peptide ratio and significantly alters the Ag+ reduction potential. Alanine replacement studies yielded insight into the sequence-function relationships of Ag nanoparticle formation, including the Ag+ coordination sites and the residues necessary for Ag synthesis. In addition, the peptide was found to function when immobilized onto surfaces, and the specific immobilizing concentration could be adjusted to yield either spherical Ag nanoparticles or high aspect ratio nanowires. These studies further illustrate the range of interesting new solid-state chemistries possible using biomolecules.
