Publications

@article{ho1999solution,

title = {Solution structure of the aminoacyl-capped oligodeoxyribonucleotide duplex (W-TGCGCAC)(2)},

author = {Ho, W C and Steinbeck, C and Richert, C},

url = {http://dx.doi.org/10.1021/bi991169w},

doi = {10.1021/bi991169w},

year  = {1999},

date = {1999-01-01},

journal = {Biochemistry},

volume = {38},

number = {39},

pages = {12597--12606},

publisher = {ACS Publications},

abstract = {Reported here is the solution structure of the aminoacyl-DNA duplex (W-TGCGCAC)(2). This duplex forms a continuously pi-stacked helix consisting of both nucleobases and amino acid side chains. According to NMR and UV analyses, the duplex melts in a cooperative transition and with 1.3-1.8% greater hyperchromicity than the control duplex (TGCGCAC)(2). A van't Hoff analysis of UV melting points at different concentrations shows that the two tryptophan residues contribute 4.8 kcal/mol to the Delta H degrees of complex formation at 10 mM salt concentration and less than 1 kcal/mol at 150 mM I salt. The entropic cost for duplex association in the presence of the amino acid residues is 13 cal/molK greater than that for the control at 10 mM salt concentration, and 3 cal/molK lower than that of the control at 0.15 ionic strength. The conformation of W-TGCGCAC in duplex form, determined via restrained torsion angle molecular dynamics, shows an undisturbed B-form DNA duplex with dangling 3'-termini. The tryptophanyl residue at the 5'-terminus packs tightly against T2 and the proximal part of adenine, without engaging in hydrogen bonding. While not providing strong enthalpic net stabilization of the duplex, the tryptophan "cap" on the duplex does seem to reduce the fraying at the termini, indicating a subtle balance of entropic and enthalpic factors contributing to the molecular dynamics. The structure also shows that, at least in the present sequence context, stacking on the terminal base pair is more favorable than intercalation, probably because the enthalpic cost associated with breaking up the stacking between DNA base pairs cannot be paid for by favorable pi-stacking interactions with the indole ring of tryptophan. These results are of importance for understanding stacking interactions in protein-DNA complexes, particularly those in enzyme-substrate complexes involving exposed nucleobases. [References: 69]},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

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Zhang, G L; Rucker, G; Breitmeier, E; Mayer, R; Steinbeck, C

Alkaloids from Thalictrum przewalskii. Journal Article

In: Planta Medica, vol. 64, no. 2, pp. 165–171, 1998.

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Steinbeck, Christoph; Richert, Clemens

The Role of Ionic Backbones in RNA Structure:~ An Unusually Stable Non-WatsontextminusCrick Duplex of a Nonionic Analog in an Apolar Medium Journal Article

In: Journal of the American Chemical Society, vol. 120, no. 45, pp. 11576–11580, 1998.

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Steinbeck, C; Spitzer, V; Starosta, M; von Poser, G

Identification of two chromenes from Calea serrata by semiautomatic structure elucidation Journal Article

In: Journal of Natural Products, vol. 60, no. 6, pp. 627–628, 1997.

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Berlin, K; Jain, R K; Tetzlaff, C; Steinbeck, C; Richert, C

Spectrometrically monitored selection experiments - quantitative laser desorption mass spectrometry of small chemical libraries Journal Article

In: Chemistry & Biology, vol. 4, no. 1, pp. 63–77, 1997.

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@article{berlin1997spectrometrically,

title = {Spectrometrically monitored selection experiments - quantitative laser desorption mass spectrometry of small chemical libraries},

author = {Berlin, K and Jain, R K and Tetzlaff, C and Steinbeck, C and Richert, C},

url = {http://dx.doi.org/10.1016/S1074-5521(97)90237-4},

doi = {10.1016/S1074-5521(97)90237-4},

year  = {1997},

date = {1997-01-01},

journal = {Chemistry & Biology},

volume = {4},

number = {1},

pages = {63--77},

publisher = {Elsevier},

abstract = {Background: Selection experiments involving chemical libraries are routinely used in the pharmaceutical industry for finding and optimizing lead compounds, In principle, almost any process involving a binding event or a reaction could be probed systematically with chemical libraries prepared by combinatorial synthesis, Traditionally, however, the vast majority of library members cannot be monitored during the selection, making a systematic correlation of structure and activity difficult, To interpret selection experiments on the level of all library components, monitoring technologies are required that give a unique and quantitative spectroscopic signal for every compound in a mixture. Results: Quantitative matrix-assisted laser desorption mass spectrometry of libraries of porphyrins and peptide-DNA hybrids consisting of 2-35 compounds is described. Porphyrin libraries were subjected to in vitro selections for liposome incorporation and binding to a protein pocket, it was shown that meso-hydroxyphenyl substituted porphyrins, known high activity photosensitizers of tumors, are preferentially incorporated in liposome membranes. A mixture of peptide-DNA hybrids was assayed for the nuclease stability of its components. Conclusions: Small libraries of non-isobaric compounds can be exhaustively or near-exhaustively monitored by mass spectrometry. Monitored selection experiments can yield detailed structure-activity maps in a single experiment, speeding up drug discovery and the probing of biochemically relevant recognition events. It is proposed that monitored assays for target binding, membrane partitioning, and biostability could be run in parallel, to select drug candidates combining several favorable properties in 'multidimensional' selection experiments. [References: 42]},

keywords = {},

pubstate = {published},

tppubtype = {article}

}