연구실개요
Our research interest in drug design encompasses three areas.
The first project is related to protein kinase C (PKC), an enzyme family that plays a pivotal role in intracellular signal transduction pathway involved in cellular processes such as cell differentiation, proliferation, modulation of gene expression and multi-drug resistance.
Based on molecular modeling analysis of crucial pharmacophores of natural PKC activators such as phorbol ester, bryostatin, ingenol, teleocidin and ebromaplysiatoxin which are expected to bind to diacylglycerol (DAG) binding site on PKC in competitive manner, we have designed and synthesized a variety of conformationally constrained DAG analogues as PKC ligands.
As a result we obtained ultrapotent DAG surrogateswith low nanomolar binding affinities for PKC-a and promising antitumor activity profile which are able potentially to be developed as novel anticancer agents.
The second one is related to vanilloid receptor (VR) which is a specific neuronal membrane recognition site for capsaicin and related irritant compounds and expressed almost exclusively by primary sensory neurons involved in nociception and neurogenic inflammation.
We have focused on the identification of ligand pharmacophores and their active conformation for eliciting agonistic or antagonistic response with resiniferatoxin (RTX), a superpotent capsaicin analog, and capsazepine as lead compounds, respectively.
These results will let us find potent VR ligands as potential analgesic and antiinflammatory agents.
The third one deals with the design and synthesis of aminoacyl t-RNA synthetase inhibitors which are emerging as attractive candidates as novel antibacterial agents to overcome serious resistance problem.
Aminoacyl-tRNA synthetases (aaRSs) are universal and essential for all living organisms.
The enzyme catalyze the transfer of a particular amino acid to its corresponding specific tRNA to form each aminoacyl-tRNAs, which are used for protein synthesis by the matching the tRNA anticodon with its cognate amino acid, resulting in faithful translation of genetic information.
Their use as drug targets can be accomplished by finding selective inhibitors of pathogen synthetases to human counterpart.
Our research has focused on the rationally designed inhibitors based on intermediates and transition states generated during enzyme reaction.
The first project is related to protein kinase C (PKC), an enzyme family that plays a pivotal role in intracellular signal transduction pathway involved in cellular processes such as cell differentiation, proliferation, modulation of gene expression and multi-drug resistance.
Based on molecular modeling analysis of crucial pharmacophores of natural PKC activators such as phorbol ester, bryostatin, ingenol, teleocidin and ebromaplysiatoxin which are expected to bind to diacylglycerol (DAG) binding site on PKC in competitive manner, we have designed and synthesized a variety of conformationally constrained DAG analogues as PKC ligands.
As a result we obtained ultrapotent DAG surrogateswith low nanomolar binding affinities for PKC-a and promising antitumor activity profile which are able potentially to be developed as novel anticancer agents.
The second one is related to vanilloid receptor (VR) which is a specific neuronal membrane recognition site for capsaicin and related irritant compounds and expressed almost exclusively by primary sensory neurons involved in nociception and neurogenic inflammation.
We have focused on the identification of ligand pharmacophores and their active conformation for eliciting agonistic or antagonistic response with resiniferatoxin (RTX), a superpotent capsaicin analog, and capsazepine as lead compounds, respectively.
These results will let us find potent VR ligands as potential analgesic and antiinflammatory agents.
The third one deals with the design and synthesis of aminoacyl t-RNA synthetase inhibitors which are emerging as attractive candidates as novel antibacterial agents to overcome serious resistance problem.
Aminoacyl-tRNA synthetases (aaRSs) are universal and essential for all living organisms.
The enzyme catalyze the transfer of a particular amino acid to its corresponding specific tRNA to form each aminoacyl-tRNAs, which are used for protein synthesis by the matching the tRNA anticodon with its cognate amino acid, resulting in faithful translation of genetic information.
Their use as drug targets can be accomplished by finding selective inhibitors of pathogen synthetases to human counterpart.
Our research has focused on the rationally designed inhibitors based on intermediates and transition states generated during enzyme reaction.