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26 results on '"Szewczyk, Jason W."'

5. Recognition of the four Watson-Crick base pairs in the DNA minor groove by synthetic ligands

Author

White, Sarah, Szewczyk, Jason W., Turner, James M., Baird, Eldon E., and Dervan, Peter B.

Subjects
DNA binding proteins -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

It has been possible to identify the DNA-binding affinities of three eight-ring hairpin polyamides containing pairings of Im/Py, Py/Im opposite G.C, C.G and either Py/Py, Hp/Py or Py/Hp at a common single point opposite T.A and A.T. A new aromatic acid, 3-hydroxypyrrole (Hp), was added to test for pairings that discriminate A.T from T.A. It was found that replacing a single hydrogen atom with a hydroxy group in a Hp/Py pairing regulates affinity and specificity by an order of magnitude.

Published
1998

7. Discovery of phenyl acetamides as potent and selective GPR119 agonists

Author

Zhu, Cheng, Wang, Liping, Zhu, Yuping, Guo, Zack Zhiqiang, Liu, Ping, Hu, Zhiyong, Szewczyk, Jason W., Kang, Ling, Chicchi, Gary, Ehrhardt, Anka, Woods, Andrea, Seo, Toru, Woods, Morgan, van Heek, Margaret, Dingley, Karen H., Pang, Jianmei, Salituro, Gino M., Powell, Joyce, Terebetski, Jenna L., Hornak, Viktor, Campeau, Louis-Charles, Orr, Robert K., Ujjainwalla, Feroze, Miller, Michael, Stamford, Andrew, Wood, Harold B., Kowalski, Timothy, Nargund, Ravi P., and Edmondson, Scott D.

Published
2017
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12. Synthesis of new four-atom-linked capped porphyrins

Author

Ma, Wuping, Wilcoxen, Keith M., Szewczyk, Jason W., and Ibers, James A.

Subjects
Porphyrins -- Research, Organic compounds -- Synthesis, Biological sciences, Chemistry
Abstract

The synthesis of two new four-atom-linked capped porphyrins H2(OC3Por) and H2(CO OC2Por) is described. The resulting porphyrins are severely encumbered due to the four linkages, each consisting of four atoms. The general method for the synthesis of the porphyrins is presented.

Published
1995

13. Design of ligands for sequence-specific recognition of the minor-major grooves of DNA

Author

Szewczyk, Jason W., Szewczyk, Jason W., Szewczyk, Jason W., and Szewczyk, Jason W.

Abstract

The two most powerful chemical approaches to date for the sequence-specific recognition of double helical DNA are the pyrrole-imidazole polyamides in the minor groove and oligonucleotide-directed triple-helix formation in the major groove. Described here are the design and synthetic methods to combine the two models for DNA recognition in a single motif. A hairpin polyamide connected to a pyrimidine-oligonucleotide via a simple aliphatic linker was shown to simultaneously recognize the major and minor grooves of DNA at subnanomolar concentrations (Chapter 2). Development of versatile solid phase methodology expanded the protocols for the synthesis of pyrrole-imidazole polyamides to include polyamide-oligonucleotide conjugates. Utilizing the pyrrole-imidazole polyamide moiety as a sequence-specific dimerization domain afforded a class of cooperative polyamide oligonucleotides which bound a 27 bp target with a 2.7 kcal mol(-1) increase in binding energy relative to the unlinked subunits (Chapter 3). Introduction of a new linker design created an extended polyamide-oligonucleotide motif to specifically target 31 contiguous base pairs of DNA at subnanomolar concentrations (Chapter 4). Polyamide-oligonucleotides combine the two binding models to create a paradigm for simultaneous recognition of the major-minor grooves of DNA with synthetic ligands. For the pyrrole-imidazole polyamide model, sequence specificity depends on side-by-side aromatic amino acid pairings. An Im/Py pair distinguishes G • C from C • G and both of these from A,T base pairs. A Py/Py pair specifies A,T from G,C but does not distinguish A•T from T•A. To break this degeneracy a new aromatic amino acid, 3-hydroxypyrrole (Hp), was synthesized to test for pairings which discriminate A • T from T • A. Replacement of a single hydrogen atom with a hydroxy group in a Hp/Py pairing regulates affinity and specificity by an order of magnitude. By incorporation of a third aromatic amino acid, hydroxypyrrole-imida

Published
1999

15. Affinity and specificity of multiple hydroxypyrrole/pyrrole ring pairings for coded recognition of DNA

Author

White, Sarah, Turner, James M., Szewczyk, Jason W., Baird, Eldon E., and Dervan, Peter B.

Subjects
Polyamides -- Research, Ring formation (Chemistry) -- Research, Proteins -- Research, DNA -- Research, Chemistry
Abstract

Three consecutive amino acid ring Hp/Py pairs can be combined in a hairpin model to specify core sequence 5'-TTA-3' from 5'-TAT-3' in the DNA minor groove. These ring pairs were used in identifying sequences in the minor groove of the DNA. Experiments found that hydroxypyrrole-imidazole-pyrrole polyamides complete the design of the minor groove recognition code. The four-ring pairs Im/Py, Py/Im, Hp/Py and Py/Hp complete the code and complement four Watson-Crick base pairs.

Published
1999

16. Cooperative triple-helix formation via a minor groove dimerization domain

Author

Szewczyk, Jason W., Baird, Eldon E., and Dervan, Peter B.

Subjects
Nucleotides -- Research, DNA binding proteins -- Research, Polyamides -- Research, Chemistry
Abstract

A pyrrole-imidazole polyamide oligonucleotide is found to bind cooperatively to a double-stranded DNA template via a sequence specific polyamide dimerization domain. Findings revealed that the unmodified oligonucleotide, 5'-d(TTTTTT(super Me)C-(super Me)CTTT)-3', binds each triple-helix site with an equilibrium association constant of 1.7 X 10(super 6)/M. The untethered polyamide ImPyPy binds to its 5'-TGTCA-3' target site with an equilibrium association constant of 1.5 X 10(super 5)/M.

Published
1996

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