Antiparallel side-by-side dimeric motif for sequence-specific recognition in the minor groove of DNA by the designed peptide 1-methylimidazole-2-carboxamide netropsin

Milan Mrksich; Warren S. Wade; Tammy J. Dwyer; Bernhard H. Geierstanger; David E. Wemmer; Peter B. Dervan

doi:10.1073/pnas.89.16.7586

Antiparallel side-by-side dimeric motif for sequence-specific recognition in the minor groove of DNA by the designed peptide 1-methylimidazole-2-carboxamide netropsin

Milan Mrksich^*, Warren S. Wade, Tammy J. Dwyer, Bernhard H. Geierstanger, David E. Wemmer, Peter B. Dervan

^*Corresponding author for this work

Biomedical Engineering

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222 Scopus citations

Abstract

The designed peptide 1-methylimidazole-2-carboxamide netropsin (2-ImN) binds specifically to the sequence 5′-TGACT-3′. Direct evidence from NMR spectroscopy is presented that this synthetic ligand binds DNA as a 2:1 complex, which reveals that the structure is an antiparallel dimer in the minor groove of DNA. This is in contrast to the 1:1 complexes usually seen with most crescent-shaped minor groove binding molecules targeted toward A+T-rich tracts but reminiscent of a dimeric motif found for distamycin at high concentrations. These results suggest that sequence-dependent groove width may play an important role in allowing an expanded set of DNA binding motifs for synthetic peptides.

Original language	English (US)
Pages (from-to)	7586-7590
Number of pages	5
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	89
Issue number	16
DOIs	https://doi.org/10.1073/pnas.89.16.7586
State	Published - Aug 15 1992

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Mrksich, M., Wade, W. S., Dwyer, T. J., Geierstanger, B. H., Wemmer, D. E., & Dervan, P. B. (1992). Antiparallel side-by-side dimeric motif for sequence-specific recognition in the minor groove of DNA by the designed peptide 1-methylimidazole-2-carboxamide netropsin. Proceedings of the National Academy of Sciences of the United States of America, 89(16), 7586-7590. https://doi.org/10.1073/pnas.89.16.7586

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title = "Antiparallel side-by-side dimeric motif for sequence-specific recognition in the minor groove of DNA by the designed peptide 1-methylimidazole-2-carboxamide netropsin",

abstract = "The designed peptide 1-methylimidazole-2-carboxamide netropsin (2-ImN) binds specifically to the sequence 5′-TGACT-3′. Direct evidence from NMR spectroscopy is presented that this synthetic ligand binds DNA as a 2:1 complex, which reveals that the structure is an antiparallel dimer in the minor groove of DNA. This is in contrast to the 1:1 complexes usually seen with most crescent-shaped minor groove binding molecules targeted toward A+T-rich tracts but reminiscent of a dimeric motif found for distamycin at high concentrations. These results suggest that sequence-dependent groove width may play an important role in allowing an expanded set of DNA binding motifs for synthetic peptides.",

author = "Milan Mrksich and Wade, {Warren S.} and Dwyer, {Tammy J.} and Geierstanger, {Bernhard H.} and Wemmer, {David E.} and Dervan, {Peter B.}",

year = "1992",

month = aug,

day = "15",

doi = "10.1073/pnas.89.16.7586",

language = "English (US)",

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Mrksich, M, Wade, WS, Dwyer, TJ, Geierstanger, BH, Wemmer, DE & Dervan, PB 1992, 'Antiparallel side-by-side dimeric motif for sequence-specific recognition in the minor groove of DNA by the designed peptide 1-methylimidazole-2-carboxamide netropsin', Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 16, pp. 7586-7590. https://doi.org/10.1073/pnas.89.16.7586

Antiparallel side-by-side dimeric motif for sequence-specific recognition in the minor groove of DNA by the designed peptide 1-methylimidazole-2-carboxamide netropsin. / Mrksich, Milan; Wade, Warren S.; Dwyer, Tammy J. et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 16, 15.08.1992, p. 7586-7590.

Research output: Contribution to journal › Article › peer-review

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T1 - Antiparallel side-by-side dimeric motif for sequence-specific recognition in the minor groove of DNA by the designed peptide 1-methylimidazole-2-carboxamide netropsin

AU - Mrksich, Milan

AU - Wade, Warren S.

AU - Dwyer, Tammy J.

AU - Geierstanger, Bernhard H.

AU - Wemmer, David E.

AU - Dervan, Peter B.

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N2 - The designed peptide 1-methylimidazole-2-carboxamide netropsin (2-ImN) binds specifically to the sequence 5′-TGACT-3′. Direct evidence from NMR spectroscopy is presented that this synthetic ligand binds DNA as a 2:1 complex, which reveals that the structure is an antiparallel dimer in the minor groove of DNA. This is in contrast to the 1:1 complexes usually seen with most crescent-shaped minor groove binding molecules targeted toward A+T-rich tracts but reminiscent of a dimeric motif found for distamycin at high concentrations. These results suggest that sequence-dependent groove width may play an important role in allowing an expanded set of DNA binding motifs for synthetic peptides.

AB - The designed peptide 1-methylimidazole-2-carboxamide netropsin (2-ImN) binds specifically to the sequence 5′-TGACT-3′. Direct evidence from NMR spectroscopy is presented that this synthetic ligand binds DNA as a 2:1 complex, which reveals that the structure is an antiparallel dimer in the minor groove of DNA. This is in contrast to the 1:1 complexes usually seen with most crescent-shaped minor groove binding molecules targeted toward A+T-rich tracts but reminiscent of a dimeric motif found for distamycin at high concentrations. These results suggest that sequence-dependent groove width may play an important role in allowing an expanded set of DNA binding motifs for synthetic peptides.

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Mrksich M, Wade WS, Dwyer TJ, Geierstanger BH, Wemmer DE, Dervan PB. Antiparallel side-by-side dimeric motif for sequence-specific recognition in the minor groove of DNA by the designed peptide 1-methylimidazole-2-carboxamide netropsin. Proceedings of the National Academy of Sciences of the United States of America. 1992 Aug 15;89(16):7586-7590. doi: 10.1073/pnas.89.16.7586

Antiparallel side-by-side dimeric motif for sequence-specific recognition in the minor groove of DNA by the designed peptide 1-methylimidazole-2-carboxamide netropsin

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