Published in ACS chemical biology
Antimycins are a family of natural products possessing outstanding biological activities and unique structures, which have intrigued chemists for over a half century. Of particular interest are the ring-expanded antimycins that show promising anticancer potential and whose biosynthesis remains uncharacterized. Specifically, neoantimycin and its ana...
Published in ACS chemical biology
Anthrabenzoxocinones (ABXs) including (-)-ABXs and (+)-ABXs are a group of bacterial FabF-specific inhibitors with potent antimicrobial activity of resistant strains. Optimization of their chemical structures is a promising method to develop potent antibiotics. Through biosynthetic investigation, we herein identified and characterized two highly pr...
Published in ACS chemical biology
Huntington's disease (HD) is a neurodegenerative disorder that is caused by abnormal expansion of CAG repeats in the HTT gene. The transcribed mutant RNA contains expanded CAG repeats that translate into a mutant huntingtin protein. This expanded CAG repeat also causes mis-splicing of pre-mRNA due to sequestration of muscle blind like-1 splicing fa...
Published in ACS chemical biology
Bacteria and archaea rely on CRISPR (clustered regularly interspaced short palindromic repeats) RNA-guided adaptive immune systems for sequence specific elimination of foreign nucleic acids. In Escherichia coli, short CRISPR-derived RNAs (crRNAs) assemble with Cas (CRISPR-associated) proteins into a 405-kilodalton multisubunit surveillance complex ...
Published in ACS chemical biology
The bacterial plant pathogen Agrobacterium tumefaciens uses quorum sensing (QS) in order to regulate the transfer of DNA into the host plant genome and this results in the induction of crown gall tumors. The deleterious results of these infections are widespread and affect many species of fruit and crops. In order to further our understanding of th...
Published in ACS chemical biology
Viral cyclin-dependent kinases (v-Cdks) functionally emulate their cellular Cdk counterparts. Such viral mimicry is an established phenomenon that we extend here through chemical genetics. Kinases contain gatekeeper residues that limit the size of molecules that can be accommodated within the enzyme active site. Mutating gatekeeper residues to smal...
Published in ACS chemical biology
A lack of target specificity has greatly hindered the success of inhibitor development against matrix metalloproteinases (MMPs) for the treatment of various cancers. The MMP catalytic domains are highly conserved, whereas the hemopexin-like domains of MMPs are unique to each family member. The hemopexin-like domain of MMP-9 enhances cancer cell mig...
Published in ACS chemical biology
Allosteric integrase inhibitors (ALLINIs) bind to the lens epithelial-derived growth factor (LEDGF) pocket on HIV-1 integrase (IN) and possess potent antiviral effects. Rather than blocking proviral integration, ALLINIs trigger IN conformational changes that have catastrophic effects on viral maturation, rendering the virions assembled in the prese...
Published in ACS chemical biology
Anabaenopeptins are a diverse group of cyclic peptides, which contain an unusual ureido linkage. Namalides are shorter structural homologues of anabaenopeptins, which also contain an ureido linkage. The biosynthetic origins of namalides are unknown despite a strong resemblance to anabaenopeptins. Here, we show the cyanobacterium Nostoc sp. CENA543 ...
Published in ACS chemical biology
The rational design of environmentally sensitive dyes with superior properties is critical for elucidating the fundamental biological processes and understanding the biophysical behavior of cell membranes. In this study, a novel group of fluorene-based push-pull probes was developed for imaging membrane lipids. The design of these fluorogenic conju...
