Congbao Kang - Academia.edu (original) (raw)

Papers by Congbao Kang

Research paper thumbnail of Discovery of Covalent Inhibitors Targeting the Transcriptional Enhanced Associate Domain Central Pocket

Journal of Medicinal Chemistry, Sep 10, 2020

We estimate a DSGE model where rare large shocks can occur, by replacing the commonly used Gaussi... more We estimate a DSGE model where rare large shocks can occur, by replacing the commonly used Gaussian assumption with a Student-t distribution. We show that the latter is strongly favored by the data in the context of the Smets and Wouters (2007) model, even when we allow for low frequency variation in the shocks' volatility. To assess the quantitative impact of rare shocks on the business cycle we perform a counterfactual experiment where we show that, absent "rare shocks", all recessions would have been of roughly the same magnitude. Further, we show that inference about low frequency changes in volatility-and in particular, inference about the magnitude of Great Moderation-is different once we allow for fat tails. Finally, we show that the evidence of fat tails is just as strong when we exclude the recent financial crisis from our sample.

Research paper thumbnail of {"__content__"=>"Backbone resonance assignment for the N-terminal region of bacterial tRNA-(NG37) methyltransferase.", "sup"=>{"__content__"=>"1"}}

Biomolecular NMR assignments, Jan 8, 2018

Bacterial tRNA (guanine-N)-methyltransferase (TrmD) is an important antibacterial target due to i... more Bacterial tRNA (guanine-N)-methyltransferase (TrmD) is an important antibacterial target due to its essential role in translation. TrmD has two domains connected with a flexible linker. The N-terminal domain (NTD) of TrmD contains the S-adenosyl-L-methionine (SAM) cofactor binding site and the C-terminal domain is critical for tRNA binding. Here we report the backbone NMR resonance assignments for NTD of Pseudomonas aeruginosa TrmD. Its secondary structure was determined based on the assigned resonances. Relaxation analysis revealed that NTD existed as dimers in solution. NTD also exhibited thermal stability in solution. Its interactions with SAM and other compounds suggest it can be used for evaluating SAM competitive inhibitors by NMR.

Research paper thumbnail of {"__content__"=>"Elucidating the bactericidal mechanism of action of the linear antimicrobial tetrapeptide BRBR-NH.", "sub"=>{"__content__"=>"2"}}

Biochimica et biophysica acta, Aug 1, 2018

Linear antimicrobial peptides, with their rapid bactericidal mode of action, are well-suited for ... more Linear antimicrobial peptides, with their rapid bactericidal mode of action, are well-suited for development as topical antibacterial drugs. We recently designed a synthetic linear 4-residue peptide, BRBR-NH, with potent bactericidal activity against Staphylococcus aureus (MIC 6.25 μM), the main causative pathogen of human skin infections with an unknown mechanism of action. Herein, we describe a series of experiments conducted to gain further insights into its mechanism of action involving electron microscopy, artificial membrane dye leakage, solution- and solid-state NMR spectroscopy followed by molecular dynamics simulations. Experimental results point towards a SMART (Soft Membranes Adapt and Respond, also Transiently) mechanism of action, suggesting that the peptide can be developed as a topical antibacterial agent for treating drug-resistant Staphylococcus aureus infections.

Research paper thumbnail of Solution structure of the transmembrane domain and the juxta-membrane domain of the Erythropoietin Receptor in micelles

with specic help available everywhere you see the i O symbol. The following versions of software ... more with specic help available everywhere you see the i O symbol. The following versions of software and data (see references i O) were used in the production of this report:

Research paper thumbnail of NMR solution structure of the N-terminal PAS domain of hERG

Research paper thumbnail of Application of Fragment-Based Drug Discovery against DNA Gyrase B

Collection of Czechoslovak Chemical Communications, Jun 24, 2015

It contains detailed isothermal titration curves of each fragment binding to E. coli gyrase B and... more It contains detailed isothermal titration curves of each fragment binding to E. coli gyrase B and experimental conditions for the synthesis of compounds 19-31.

Research paper thumbnail of Structural and dynamic studies of DENV and ZIKV proteases and its insight into inhibitor design

Journal of Proteomics & Bioinformatics, Oct 6, 2017

Research paper thumbnail of Targeting <scp>RNA</scp>‐binding proteins with small molecules: perspectives, pitfalls and bifunctional molecules

FEBS Letters, Jul 30, 2023

RNA‐binding proteins (RBPs) play vital roles in organisms through binding with RNAs to regulate t... more RNA‐binding proteins (RBPs) play vital roles in organisms through binding with RNAs to regulate their functions. Small molecules affecting the function of RBPs have been developed, providing new avenues for drug discovery. Herein, we describe the perspectives on developing small molecule regulators of RBPs. The following types of small molecule modulators are of great interest in drug discovery: small molecules binding to RBPs to affect interactions with RNA molecules, bifunctional molecules binding to RNA or RBP to influence their interactions, and other types of molecules that affect the stability of RNA or RBPs. Moreover, we emphasize that the bifunctional molecules may play important roles in small molecule development to overcome the challenges encountered in the process of drug discovery.

Research paper thumbnail of Backbone assignment of an unlinked NS2B and NS3 protease complex of dengue virus 2

Journal of Back and Musculoskeletal Rehabilitation, Jun 4, 2013

Research paper thumbnail of Backbone resonance assignment for the N-terminal region of bacterial tRNA-(N1G37) methyltransferase

Biomolecular Nmr Assignments, Oct 8, 2018

Bacterial tRNA (guanine37-N 1)-methyltransferase (TrmD) plays important roles in translation, mak... more Bacterial tRNA (guanine37-N 1)-methyltransferase (TrmD) plays important roles in translation, making it an important target for the development of new antibacterial compounds. TrmD comprises two domains with the N-terminal domain binding to the S-adenosyl-L-methionine (SAM) cofactor and the C-terminal domain critical for tRNA binding. Bacterial TrmD is functional as a dimer. Here we report the backbone NMR resonance assignments for the full length TrmD protein of Pseudomonas aeruginosa. Most resonances were assigned and the secondary structure for each amino acid was determined according to the assigned backbone resonances. The availability of the assignment will be valuable for exploring molecular interactions of TrmD with ligands, inhibitors and tRNA. Keywords: TrmD · Pseudomonas aeruginosa · tRNA methyltransferase · epitranscriptome · drug discovery · antibacterial · protein dynamics · backbone assignment

Research paper thumbnail of Identification of covalent active site inhibitors of dengue virus protease

Drug Design Development and Therapy, Dec 1, 2015

Dengue virus (DENV) protease is an attractive target for drug development; however, no compounds ... more Dengue virus (DENV) protease is an attractive target for drug development; however, no compounds have reached clinical development to date. In this study, we utilized a potent West Nile virus protease inhibitor of the pyrazole ester derivative class as a chemical starting point for DENV protease drug development. Compound potency and selectivity for DENV protease were improved through structure-guided small molecule optimization, and proteaseinhibitor binding interactions were validated biophysically using nuclear magnetic resonance. Our work strongly suggests that this class of compounds inhibits flavivirus protease through targeted covalent modification of active site serine, contrary to an allosteric binding mechanism as previously described.

Research paper thumbnail of 1H, 13C and 15N Chemical Shift Assignment Assignment of Human Membrane Protein KCNE3 in LMPC micelles

Journal of Back and Musculoskeletal Rehabilitation, Feb 11, 2010

Research paper thumbnail of Assignment of the transmembrane domain of the erythropoietin receptor

Journal of Back and Musculoskeletal Rehabilitation, Dec 8, 2014

Research paper thumbnail of Structure of the transmembrane domain of the mouse erythropoietin receptor

Research paper thumbnail of NMR Structural Study of the Domains of the KCNH Channels and its Insight into Channel Gating

Biophysical Journal, 2014

channel function. Our results show that Mg 2þ and Ba 2þ binding to the high affinity Ca 2þ bindin... more channel function. Our results show that Mg 2þ and Ba 2þ binding to the high affinity Ca 2þ binding site (Calcium Bowl) also induce structural rearrangements of the gating ring, although to a lesser extent than those observed after Ca 2þ binding. All the same, these rearrangements are not strictly coupled to the opening of the pore. Structural changes of the gating ring induced by Ca 2þ , Mg 2þ and Ba 2þ show different magnitude and voltage-dependence. These results indicate the existence of a complex movement of the gating ring induced by the binding of divalent cations to the calcium bowl.

Research paper thumbnail of EPR Spectroscopic Studies on the Structural and Dynamic Properties of Human KCNE1 Membrane Protein in Lipid Bilayers

Biophysical Journal, 2010

For electron paramagnetic resonance (EPR) spectroscopic studies, the TOAC spin label offers the u... more For electron paramagnetic resonance (EPR) spectroscopic studies, the TOAC spin label offers the unique advantage over other conventional labels in that it reports accurate backbone motion and peptide dynamics due to its rigid nature. This label has become extremely important in EPR studies to study membrane protein topology and their associated dynamics. Additionally, some researches have also developed spectroscopic techniques using magnetically aligned (bicelles) and mechanically aligned (glass plates) lipid samples to extract additional information directly related to structural topology with respect to the membrane. Based upon the samples orientation, other anisotropic spectral parameters can also be determined. EPR spectroscopy offers a unique solution due to the fact it has a much higher sensitivity and also a different frequency domain than other conventional techniques. Thus, we have performed EPR alignment studies on two-model peptides magainin-2 and the M2d subunit of the acetylcholine receptor. Both of these peptides have been well characterized and are 23 amino acids in length.

Research paper thumbnail of Molecular and structural characterization of the domain 2 of hepatitis C virus non-structural protein 5A

PubMed, Aug 31, 2006

Hepatitis C virus (HCV) non-structural protein 5A protein (NS5A), which consists of three functio... more Hepatitis C virus (HCV) non-structural protein 5A protein (NS5A), which consists of three functional domains, is involved in regulating viral replication, interferon resistance, and apoptosis. Recently, the three-dimensional structure of the domain 1 was determined. However, currently the molecular basis for the domains 2 and 3 of HCV NS5A is yet to be defined. Toward this end, we expressed, purified the domain 2 of the NS5A (NS5A-D2), and then performed biochemical and structural studies. The purified domain 2 was active and was able to bind NS5B and PKR, biological partners of NS5A. The results from gel filtration, CD analysis, 1D 1H NMR and 2D 1H-15N heteronuclear single quantum correlation (HSQC) spectroscopy indicate that the domain 2 of NS5A appears to be flexible and disordered.

Research paper thumbnail of Elucidating the bactericidal mechanism of action of the linear antimicrobial tetrapeptide BRBR-NH2

Biochimica Et Biophysica Acta - Biomembranes, Aug 1, 2018

Linear antimicrobial peptides, with their rapid bactericidal mode of action, are wellsuited for d... more Linear antimicrobial peptides, with their rapid bactericidal mode of action, are wellsuited for development as topical antibacterial drugs. We recently designed a synthetic linear 4-residue peptide, BRBR-NH2, with potent bactericidal activity against Staphylococcus aureus (MIC 6.25 µM), the main causative pathogen of human skin infections with an unknown mechanism of action. Herein, we describe a series of experiments conducted to gain further insights into its mechanism of action involving electron microscopy, artificial membrane dye leakage, solution-and solid-state NMR spectroscopy followed by molecular dynamics simulations. Experimental results point towards a SMART (Soft Membranes Adapt and Respond, also Transiently) mechanism of action, suggesting that the peptide can be developed as a topical antibacterial agent for treating drug-resistant Staphylococcus aureus infections.

Research paper thumbnail of Characterization of molecular interactions between Zika virus protease and peptides derived from the C-terminus of NS2B

Biochemical and Biophysical Research Communications, Sep 1, 2018

Zika virus (ZIKV) protease is a two-component complex in which NS3 contains the catalytic triad a... more Zika virus (ZIKV) protease is a two-component complex in which NS3 contains the catalytic triad and NS2B cofactor region is important for protease folding and activity. A protease construct-eZiPro without the transmembrane domains of NS2B was designed. Structural study on eZiPro reveals that the Thr-Gly-Lys-Arg (TGKR) sequence at the C-terminus of NS2B binds to the active site after cleavage. The bZiPro construct only contains NS2B cofactor region and the N-terminus of NS3 without any artificial linker or protease cleavage site, giving rise to an empty pocket accessible to substrate and inhibitor binding. Herein, we demonstrate that the TGKR sequence of NS2B in eZiPro is dynamic. Peptides from NS2B with various lengths exhibit different binding affinities to bZiPro. TGKR binding to the active site in eZiPro does not affect protease binding to small-molecule compounds. Our results suggest that eZiPro will also be useful for evaluating small-molecule protease inhibitors.

Research paper thumbnail of <sup>19</sup>F-NMR in Target-based Drug Discovery

Current Medicinal Chemistry, Oct 22, 2019

Research paper thumbnail of Discovery of Covalent Inhibitors Targeting the Transcriptional Enhanced Associate Domain Central Pocket

Journal of Medicinal Chemistry, Sep 10, 2020

We estimate a DSGE model where rare large shocks can occur, by replacing the commonly used Gaussi... more We estimate a DSGE model where rare large shocks can occur, by replacing the commonly used Gaussian assumption with a Student-t distribution. We show that the latter is strongly favored by the data in the context of the Smets and Wouters (2007) model, even when we allow for low frequency variation in the shocks' volatility. To assess the quantitative impact of rare shocks on the business cycle we perform a counterfactual experiment where we show that, absent "rare shocks", all recessions would have been of roughly the same magnitude. Further, we show that inference about low frequency changes in volatility-and in particular, inference about the magnitude of Great Moderation-is different once we allow for fat tails. Finally, we show that the evidence of fat tails is just as strong when we exclude the recent financial crisis from our sample.

Research paper thumbnail of {"__content__"=>"Backbone resonance assignment for the N-terminal region of bacterial tRNA-(NG37) methyltransferase.", "sup"=>{"__content__"=>"1"}}

Biomolecular NMR assignments, Jan 8, 2018

Bacterial tRNA (guanine-N)-methyltransferase (TrmD) is an important antibacterial target due to i... more Bacterial tRNA (guanine-N)-methyltransferase (TrmD) is an important antibacterial target due to its essential role in translation. TrmD has two domains connected with a flexible linker. The N-terminal domain (NTD) of TrmD contains the S-adenosyl-L-methionine (SAM) cofactor binding site and the C-terminal domain is critical for tRNA binding. Here we report the backbone NMR resonance assignments for NTD of Pseudomonas aeruginosa TrmD. Its secondary structure was determined based on the assigned resonances. Relaxation analysis revealed that NTD existed as dimers in solution. NTD also exhibited thermal stability in solution. Its interactions with SAM and other compounds suggest it can be used for evaluating SAM competitive inhibitors by NMR.

Research paper thumbnail of {"__content__"=>"Elucidating the bactericidal mechanism of action of the linear antimicrobial tetrapeptide BRBR-NH.", "sub"=>{"__content__"=>"2"}}

Biochimica et biophysica acta, Aug 1, 2018

Linear antimicrobial peptides, with their rapid bactericidal mode of action, are well-suited for ... more Linear antimicrobial peptides, with their rapid bactericidal mode of action, are well-suited for development as topical antibacterial drugs. We recently designed a synthetic linear 4-residue peptide, BRBR-NH, with potent bactericidal activity against Staphylococcus aureus (MIC 6.25 μM), the main causative pathogen of human skin infections with an unknown mechanism of action. Herein, we describe a series of experiments conducted to gain further insights into its mechanism of action involving electron microscopy, artificial membrane dye leakage, solution- and solid-state NMR spectroscopy followed by molecular dynamics simulations. Experimental results point towards a SMART (Soft Membranes Adapt and Respond, also Transiently) mechanism of action, suggesting that the peptide can be developed as a topical antibacterial agent for treating drug-resistant Staphylococcus aureus infections.

Research paper thumbnail of Solution structure of the transmembrane domain and the juxta-membrane domain of the Erythropoietin Receptor in micelles

with specic help available everywhere you see the i O symbol. The following versions of software ... more with specic help available everywhere you see the i O symbol. The following versions of software and data (see references i O) were used in the production of this report:

Research paper thumbnail of NMR solution structure of the N-terminal PAS domain of hERG

Research paper thumbnail of Application of Fragment-Based Drug Discovery against DNA Gyrase B

Collection of Czechoslovak Chemical Communications, Jun 24, 2015

It contains detailed isothermal titration curves of each fragment binding to E. coli gyrase B and... more It contains detailed isothermal titration curves of each fragment binding to E. coli gyrase B and experimental conditions for the synthesis of compounds 19-31.

Research paper thumbnail of Structural and dynamic studies of DENV and ZIKV proteases and its insight into inhibitor design

Journal of Proteomics & Bioinformatics, Oct 6, 2017

Research paper thumbnail of Targeting <scp>RNA</scp>‐binding proteins with small molecules: perspectives, pitfalls and bifunctional molecules

FEBS Letters, Jul 30, 2023

RNA‐binding proteins (RBPs) play vital roles in organisms through binding with RNAs to regulate t... more RNA‐binding proteins (RBPs) play vital roles in organisms through binding with RNAs to regulate their functions. Small molecules affecting the function of RBPs have been developed, providing new avenues for drug discovery. Herein, we describe the perspectives on developing small molecule regulators of RBPs. The following types of small molecule modulators are of great interest in drug discovery: small molecules binding to RBPs to affect interactions with RNA molecules, bifunctional molecules binding to RNA or RBP to influence their interactions, and other types of molecules that affect the stability of RNA or RBPs. Moreover, we emphasize that the bifunctional molecules may play important roles in small molecule development to overcome the challenges encountered in the process of drug discovery.

Research paper thumbnail of Backbone assignment of an unlinked NS2B and NS3 protease complex of dengue virus 2

Journal of Back and Musculoskeletal Rehabilitation, Jun 4, 2013

Research paper thumbnail of Backbone resonance assignment for the N-terminal region of bacterial tRNA-(N1G37) methyltransferase

Biomolecular Nmr Assignments, Oct 8, 2018

Bacterial tRNA (guanine37-N 1)-methyltransferase (TrmD) plays important roles in translation, mak... more Bacterial tRNA (guanine37-N 1)-methyltransferase (TrmD) plays important roles in translation, making it an important target for the development of new antibacterial compounds. TrmD comprises two domains with the N-terminal domain binding to the S-adenosyl-L-methionine (SAM) cofactor and the C-terminal domain critical for tRNA binding. Bacterial TrmD is functional as a dimer. Here we report the backbone NMR resonance assignments for the full length TrmD protein of Pseudomonas aeruginosa. Most resonances were assigned and the secondary structure for each amino acid was determined according to the assigned backbone resonances. The availability of the assignment will be valuable for exploring molecular interactions of TrmD with ligands, inhibitors and tRNA. Keywords: TrmD · Pseudomonas aeruginosa · tRNA methyltransferase · epitranscriptome · drug discovery · antibacterial · protein dynamics · backbone assignment

Research paper thumbnail of Identification of covalent active site inhibitors of dengue virus protease

Drug Design Development and Therapy, Dec 1, 2015

Dengue virus (DENV) protease is an attractive target for drug development; however, no compounds ... more Dengue virus (DENV) protease is an attractive target for drug development; however, no compounds have reached clinical development to date. In this study, we utilized a potent West Nile virus protease inhibitor of the pyrazole ester derivative class as a chemical starting point for DENV protease drug development. Compound potency and selectivity for DENV protease were improved through structure-guided small molecule optimization, and proteaseinhibitor binding interactions were validated biophysically using nuclear magnetic resonance. Our work strongly suggests that this class of compounds inhibits flavivirus protease through targeted covalent modification of active site serine, contrary to an allosteric binding mechanism as previously described.

Research paper thumbnail of 1H, 13C and 15N Chemical Shift Assignment Assignment of Human Membrane Protein KCNE3 in LMPC micelles

Journal of Back and Musculoskeletal Rehabilitation, Feb 11, 2010

Research paper thumbnail of Assignment of the transmembrane domain of the erythropoietin receptor

Journal of Back and Musculoskeletal Rehabilitation, Dec 8, 2014

Research paper thumbnail of Structure of the transmembrane domain of the mouse erythropoietin receptor

Research paper thumbnail of NMR Structural Study of the Domains of the KCNH Channels and its Insight into Channel Gating

Biophysical Journal, 2014

channel function. Our results show that Mg 2þ and Ba 2þ binding to the high affinity Ca 2þ bindin... more channel function. Our results show that Mg 2þ and Ba 2þ binding to the high affinity Ca 2þ binding site (Calcium Bowl) also induce structural rearrangements of the gating ring, although to a lesser extent than those observed after Ca 2þ binding. All the same, these rearrangements are not strictly coupled to the opening of the pore. Structural changes of the gating ring induced by Ca 2þ , Mg 2þ and Ba 2þ show different magnitude and voltage-dependence. These results indicate the existence of a complex movement of the gating ring induced by the binding of divalent cations to the calcium bowl.

Research paper thumbnail of EPR Spectroscopic Studies on the Structural and Dynamic Properties of Human KCNE1 Membrane Protein in Lipid Bilayers

Biophysical Journal, 2010

For electron paramagnetic resonance (EPR) spectroscopic studies, the TOAC spin label offers the u... more For electron paramagnetic resonance (EPR) spectroscopic studies, the TOAC spin label offers the unique advantage over other conventional labels in that it reports accurate backbone motion and peptide dynamics due to its rigid nature. This label has become extremely important in EPR studies to study membrane protein topology and their associated dynamics. Additionally, some researches have also developed spectroscopic techniques using magnetically aligned (bicelles) and mechanically aligned (glass plates) lipid samples to extract additional information directly related to structural topology with respect to the membrane. Based upon the samples orientation, other anisotropic spectral parameters can also be determined. EPR spectroscopy offers a unique solution due to the fact it has a much higher sensitivity and also a different frequency domain than other conventional techniques. Thus, we have performed EPR alignment studies on two-model peptides magainin-2 and the M2d subunit of the acetylcholine receptor. Both of these peptides have been well characterized and are 23 amino acids in length.

Research paper thumbnail of Molecular and structural characterization of the domain 2 of hepatitis C virus non-structural protein 5A

PubMed, Aug 31, 2006

Hepatitis C virus (HCV) non-structural protein 5A protein (NS5A), which consists of three functio... more Hepatitis C virus (HCV) non-structural protein 5A protein (NS5A), which consists of three functional domains, is involved in regulating viral replication, interferon resistance, and apoptosis. Recently, the three-dimensional structure of the domain 1 was determined. However, currently the molecular basis for the domains 2 and 3 of HCV NS5A is yet to be defined. Toward this end, we expressed, purified the domain 2 of the NS5A (NS5A-D2), and then performed biochemical and structural studies. The purified domain 2 was active and was able to bind NS5B and PKR, biological partners of NS5A. The results from gel filtration, CD analysis, 1D 1H NMR and 2D 1H-15N heteronuclear single quantum correlation (HSQC) spectroscopy indicate that the domain 2 of NS5A appears to be flexible and disordered.

Research paper thumbnail of Elucidating the bactericidal mechanism of action of the linear antimicrobial tetrapeptide BRBR-NH2

Biochimica Et Biophysica Acta - Biomembranes, Aug 1, 2018

Linear antimicrobial peptides, with their rapid bactericidal mode of action, are wellsuited for d... more Linear antimicrobial peptides, with their rapid bactericidal mode of action, are wellsuited for development as topical antibacterial drugs. We recently designed a synthetic linear 4-residue peptide, BRBR-NH2, with potent bactericidal activity against Staphylococcus aureus (MIC 6.25 µM), the main causative pathogen of human skin infections with an unknown mechanism of action. Herein, we describe a series of experiments conducted to gain further insights into its mechanism of action involving electron microscopy, artificial membrane dye leakage, solution-and solid-state NMR spectroscopy followed by molecular dynamics simulations. Experimental results point towards a SMART (Soft Membranes Adapt and Respond, also Transiently) mechanism of action, suggesting that the peptide can be developed as a topical antibacterial agent for treating drug-resistant Staphylococcus aureus infections.

Research paper thumbnail of Characterization of molecular interactions between Zika virus protease and peptides derived from the C-terminus of NS2B

Biochemical and Biophysical Research Communications, Sep 1, 2018

Zika virus (ZIKV) protease is a two-component complex in which NS3 contains the catalytic triad a... more Zika virus (ZIKV) protease is a two-component complex in which NS3 contains the catalytic triad and NS2B cofactor region is important for protease folding and activity. A protease construct-eZiPro without the transmembrane domains of NS2B was designed. Structural study on eZiPro reveals that the Thr-Gly-Lys-Arg (TGKR) sequence at the C-terminus of NS2B binds to the active site after cleavage. The bZiPro construct only contains NS2B cofactor region and the N-terminus of NS3 without any artificial linker or protease cleavage site, giving rise to an empty pocket accessible to substrate and inhibitor binding. Herein, we demonstrate that the TGKR sequence of NS2B in eZiPro is dynamic. Peptides from NS2B with various lengths exhibit different binding affinities to bZiPro. TGKR binding to the active site in eZiPro does not affect protease binding to small-molecule compounds. Our results suggest that eZiPro will also be useful for evaluating small-molecule protease inhibitors.

Research paper thumbnail of <sup>19</sup>F-NMR in Target-based Drug Discovery

Current Medicinal Chemistry, Oct 22, 2019