David J Detlefsen

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The 21-amino acid peptides siamycin II (BMY-29303) and siamycin I (BMY-29304), derived from Streptomyces strains AA3891 and AA6532, respectively, have been found to inhibit HIV-1 fusion and viral replication in cell culture. The primary sequence of siamycin II is CLGIGSCNDFAGCGYAIVCFW. Siamycin I differs by only one amino acid; it has a valine residue at(More)
A new method for studying cellular uptake has been developed. This method is based on selected reaction monitoring liquid chromatography tandem mass spectrometry analysis of preparations from cell culture. The limit of detection for paclitaxel was approximately 0.1 microM intracellular concentration. This method has been utilized to study the uptake of(More)
The solution structure of Fe(II) cytochrome c551 from Pseudomonas aeruginosa based on 2D 1H NMR data is reported. Two sets of structure calculations were completed with a combination of simulated annealing and distance geometry calculations: one set of 20 structures included the heme-peptide covalent linkages, and one set of 10 structures excluded them. The(More)
The principles and parameters to consider when choosing an NMR probe for analysis of a volume- or mass-limited sample are identified and discussed. In particular, a capillary-based microflow probe is described which has a mass sensitivity comparable to cryoprobes (observe volume approximately 40 microL), but with several distinct advantages. The microflow(More)
Molecular flexibility is a factor that is not extensively studied in most pharmaceutical research efforts. When it is, the level of effort is high involving the preparation of detailed models supported by either molecular dynamics simulations and/or Nuclear Magnetic Resonance data. While these studies are both powerful and illuminating, they cannot be(More)
Structural studies of globular proteins by nmr can be enhanced by the use of isotope enrichment. We have been working with proteins enriched with 15N, and with both 15N and 13C. Due to the isotope enrichment we could assign several large proteins with up to 186 residues and could address structural questions. Furthermore, we can accurately measure(More)
Sequence-specific 1H NMR resonance assignments for all but the C-terminal Lys 82 are reported for iron(II) cytochrome c551 from Pseudomonas aeruginosa at 25 degrees C and pH = 6.8. Spin systems were identified by using TOCSY and DQF-COSY spectra in 2H2O and 1H2O. Sequential assignments were made by using NOESY connectivities between adjacent amide, alpha,(More)
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