This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Beta-hairpin model systems have been used to identify several factors that are crucial to antiparallel beta -sheet stability, including the conformational propensity of the loop-forming segment and sidechain-sidechain interactions between neighboring strands. We are interested in probing the factors that contribute to parallel beta -sheet stability. One of these peptides is an important part of that work. We have examined this peptide on our INOVA-600, but poor S/N has been problematic for many experiments.The other peptide we plan to examine is a beta -peptide comprised of cyclically constrained beta -amino acid residues. The study of unnatural oligomers that display secondary structural behavior analogous to that of proteins or nucleic acids provides new insight on the parameters that influence the 'foldability' of a backbone, e.g., the relationships between conformational stability and number of residues or residue flexibility. This peptide gives a characteristic CD signature for a well-characterized beta -peptide helical conformation, but no non-sequential NOEs are observed in the 2D experiments performed on our Inova 600. We expect that the increased sensitivity of experiments performed on the cryoprobe will prove useful in identifying non-sequential NOEs and provide evidence for secondary structure complementary to the CD data.We anticipate running a TOCSY and ROESY on each of the peptides and an HSQC on one of the two peptides. Our reason for running ROESY experiments on both of the compounds is two-fold. First, we are interested in examining non-sequential NOEs in these compounds, which has not been possible due to poor S/N. Second, we are curious about the capability of water suppression with ROESY using the cryoprobe. We are not aware of anyone having done this. HSQC experiments have also been difficult to acquire on our peptides at natural abundance due to poor S/N. We anticipate that using the cryoprobe will begin to resolve this problem.
Showing the most recent 10 out of 613 publications
