NMR studies on YSPTSPSY: implications for the design of DNA bisintercalators

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Abstract
NMR (600 MHz) studies on YSPTSPSY (1), the heptad repeat unit of RNA polymerase II with an extra tyrosine added to the N-terminus, show that the peptide is partially structured in aqueous solution. Peptide 1 contains two overlapping SPXX sequences and has been reported to bind to DNA by bisintercalation (Suzuki, M. Nature 1990, 344, 562-565). In 90% H2O solution at pH 3.2, the major species, which is present in > 90%, contains Pro3 and Pro6 in the trans conformation. At low temperature (4 degrees C), NOE connectivities are consistent with the presence of beta-turn structures in equilibrium with unfolded forms of the peptide. A strong dNN connectivity between Thr4/Ser5, a d alpha N connectivity between Pro3/Thr4, and a medium-range NOE between Pro3 alpha and Ser5 NH indicate the presence of a beta-turn formed by (i) Ser2-Pro3-Thr4-Ser5. A strong dNN connectivity between Ser7/Tyr8 and weaker dN delta NOE connectivities between Ser2/Pro3 delta and Ser7/Pro6 delta were also detected. The solution conformation of the peptide appears to have a crucial role in determining the interaction of the peptide with DNA, given that only bisintercalation has been reported in DNA-binding studies on 1 (Suzuki, M. Nature 1990, 344, 562-565). On the basis of these results, the peptide unit--SPTSPS--(3) has considerable potential as a structured linker in the preparation of DNA bisintercalators of the general structure Xaa-SPTSPS-Zaa (2) with improved selectivity properties.

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