ABSTRACT
Spontaneous asymmetric generation of supramolecular chiral fibers was observed in the folding induced self-assembly of a lock-washer shaped foldamer. A secondary nucleation growth mechanism is proposed to explain the observed chiral amplification or deracemization of these supramolecular fibers.
ABSTRACT
Chemotherapies, HIV infections, and treatments to block organ transplant rejection are creating a population of immunocompromised individuals at serious risk of systemic fungal infections. Since single-agent therapies are susceptible to failure due to either inherent or acquired resistance, alternative therapeutic approaches such as multi-agent therapies are needed. We have developed a bioinformatics-driven approach that efficiently predicts compound synergy for such combinatorial therapies. The approach uses chemogenomic profiles in order to identify compound profiles that have a statistically significant degree of similarity to a fluconazole profile. The compounds identified were then experimentally verified to be synergistic with fluconazole and with each other, in both Saccharomyces cerevisiae and the fungal pathogen Candida albicans. Our method is therefore capable of accurately predicting compound synergy to aid the development of combinatorial antifungal therapies.
Subject(s)
Antifungal Agents/pharmacology , Candida albicans/drug effects , Computational Biology , Computer-Aided Design , Drug Design , Fluconazole/pharmacology , Saccharomyces cerevisiae/drug effects , Animals , Antifungal Agents/chemistry , Antifungal Agents/therapeutic use , Candida albicans/genetics , Candida albicans/growth & development , Dose-Response Relationship, Drug , Drug Resistance, Fungal/genetics , Drug Synergism , Drug Therapy, Combination , Fluconazole/chemistry , Fluconazole/therapeutic use , Gene Expression Regulation, Fungal , Humans , Models, Molecular , Molecular Structure , Reproducibility of Results , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/growth & development , Structure-Activity RelationshipABSTRACT
Complete asymmetric amplification of ethylenediammonium sulfate was achieved under continuous dissolution/crystallization conditions using an abrasion/grinding method.
