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Medicinal-Pharmaceutical Chemistry

Selected Works

Selected Works

Articles 1 - 5 of 5

Full-Text Articles in Chemicals and Drugs

Dengue Virus Ns2b/Ns3 Protease Inhibitors Exploiting The Prime Side, Kuan-Hung Lin, Akbar Ali, Linah Rusere, Djade I. Soumana, Nese Kurt Yilmaz, Celia A. Schiffer Jul 2017

Dengue Virus Ns2b/Ns3 Protease Inhibitors Exploiting The Prime Side, Kuan-Hung Lin, Akbar Ali, Linah Rusere, Djade I. Soumana, Nese Kurt Yilmaz, Celia A. Schiffer

Celia A. Schiffer

The mosquito-transmitted dengue virus (DENV) infects millions of people in tropical and subtropical regions. Maturation of DENV particles requires proper cleavage of the viral polyprotein, including processing of 8 of the 13 substrate cleavage sites by dengue virus NS2B/NS3 protease. With no available direct-acting antiviral targeting DENV, NS2/NS3 protease is a promising target for inhibitor design. Current design efforts focus on the nonprime side of the DENV protease active site, resulting in highly hydrophilic and nonspecific scaffolds. However, the prime side also significantly modulates DENV protease binding affinity, as revealed by engineering the binding loop of aprotinin, a small protein …

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Interdependence Of Inhibitor Recognition In Hiv-1 Protease, Janet L. Paulsen, Florian Leidner, Debra A. Ragland, Nese Kurt Yilmaz, Celia A. Schiffer Jun 2017

Interdependence Of Inhibitor Recognition In Hiv-1 Protease, Janet L. Paulsen, Florian Leidner, Debra A. Ragland, Nese Kurt Yilmaz, Celia A. Schiffer

Celia A. Schiffer

Molecular recognition is a highly interdependent process. Subsite couplings within the active site of proteases are most often revealed through conditional amino acid preferences in substrate recognition. However, the potential effect of these couplings on inhibition and thus inhibitor design is largely unexplored. The present study examines the interdependency of subsites in HIV-1 protease using a focused library of protease inhibitors, to aid in future inhibitor design. Previously a series of darunavir (DRV) analogs was designed to systematically probe the S1' and S2' subsites. Co-crystal structures of these analogs with HIV-1 protease provide the ideal opportunity to probe subsite interdependency. …

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Methyl Transfer By Substrate Signaling From A Knotted Protein Fold, Thomas Christian, Reiko Sakaguchi, Agata P. Perlinska, George Lahoud, Takuhiro Ito, Erika A. Taylor, Shigeyuki Yokoyama, Joanna I. Sulkowska, Ya-Ming Hou Dec 2015

Methyl Transfer By Substrate Signaling From A Knotted Protein Fold, Thomas Christian, Reiko Sakaguchi, Agata P. Perlinska, George Lahoud, Takuhiro Ito, Erika A. Taylor, Shigeyuki Yokoyama, Joanna I. Sulkowska, Ya-Ming Hou

Erika A. Taylor, Ph.D.

Proteins with knotted configurations, in comparison with unknotted proteins, are restricted in conformational space. Little is known regarding whether knotted proteins have sufficient dynamics to communicate between spatially separated substrate-binding sites. TrmD is a bacterial methyltransferase that uses a knotted protein fold to catalyze methyl transfer from S-adenosyl methionine (AdoMet) to G37-tRNA. The product, m1G37-tRNA, is essential for life and maintains protein-synthesis reading frames. Using an integrated approach of structural, kinetic, and computational analysis, we show that the structurally constrained TrmD knot is required for its catalytic activity. Unexpectedly, the TrmD knot undergoes complex internal movements that respond to AdoMet …

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Interrogating Metabolism In Brain Cancer, Travis Salzillo, Jingzhe Hu, Linda Nguyen, Nicholas Whiting, Jaehyuk Lee, Joseph Weygand, Prasanta Dutta, Shivanand Pudakalakatti, Niki Zacharias Millward, Seth Gammon, Frederick F. Lang, Amy B. Heimberger, Pratip Bhattacharya Dec 2015

Interrogating Metabolism In Brain Cancer, Travis Salzillo, Jingzhe Hu, Linda Nguyen, Nicholas Whiting, Jaehyuk Lee, Joseph Weygand, Prasanta Dutta, Shivanand Pudakalakatti, Niki Zacharias Millward, Seth Gammon, Frederick F. Lang, Amy B. Heimberger, Pratip Bhattacharya

Nicholas Whiting

Many existing and emerging techniques of interrogating metabolism in brain cancer are at an early stage of development. A few clinical trials that employ these techniques are in progress in patients with brain cancer to establish the clinical efficacy of these techniques. It is likely that in vivo metabolomics and metabolic imaging is the next frontier in brain cancer diagnosis and assessing therapeutic efficacy.

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Parallel Text Immersion, Daniel P. Becker Ph.D. Dec 2011

Parallel Text Immersion, Daniel P. Becker Ph.D.

Daniel P. Becker

A new method of teaching foreign languages to beginning, intermediate, and advancing foreign language students is proposed involving reading out loud passages, chapters, and entire works of literature that are familiar to the student through required pre-reading in the students’ mother tongue. Testing is proposed to evaluate the success of the method.

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