The investigators propose a collaboration between UCSF and the Institute of Molecular Biology, Russian Academy of Sciences, Moscow, in the area of sequence- specific recognition of DNA. This effort will combine the synthetic capabilities of the Moscow group with NMR analysis expertise of the UCSF group. In this project, the Moscow group will synthesize a series of new, sequence-specific oligopeptide ligands and characterize their interaction with DNA using spectrophotometric techniques while the UCSF group will carry out high resolution NMR studies with the peptide DNA complexes. Preliminary data indicate that combining the AT specific properties of the netropsin-type structure with the GC specific properties of certain oligopeptides can create ligands which recognize particular sequences of AT and GC base pairs. In order to understand the structural basis for this sequence-specific recognition, they plan to carry out two-dimensional NMR analysis of the complex formed between these ligands and a short oligonucleotide duplex containing their preferred base-pair sequence. Results from these experiments should provide a detailed structure for these ligand-DNA complexes and lead to the design and synthesis of additional compounds with different specificity, whose DNA interactions will also be investigated. These compounds have potential as gene regulating and cancer chemotherapeutic agents as well as models for recognition of DNA by proteins.
|Mikheikin, A L; Zhuze, A L; Zasedatelev, A S (2000) Binding of symmetrical cyanine dyes into the DNA minor groove. J Biomol Struct Dyn 18:59-72|
|Nikolaev, V A; Grokhovsky, S L; Surovaya, A N et al. (1996) Design of sequence-specific DNA binding ligands that use a two-stranded peptide motif for DNA sequence recognition. J Biomol Struct Dyn 14:31-47|
|Zasedatelev, A S; Borodulin, V B; Grokhovsky, S L et al. (1995) Mono-, di- and trimeric binding of a bis-netropsin to DNA. FEBS Lett 375:304-6|
|Salmanova, D V; Nikitin, A M; Zhuze, A L et al. (1995) [Interaction of synthetic ligands containing N,4-disubstituted mono- and diphthalimides with DNA] Mol Biol (Mosk) 29:848-61|