The accessibility calculations did not include tightly bound water molecules or cations. The inclusion of water and cations may bring the predictions closer to the observed results. The cleavage at residue G8 in the TGT loop is preferentially altered by the PF-4217903 c-Met inhibitor addition of NMM. The binding could be to the top quartet formed by residues 1, 6, 10, 15 or to the TGT loop. We have previously shown that NMM binding does not significantly change the CD spectrum of the 15 mer. The CD result MK-2206 indicate that NMM binding does not alter the folding pattern of this DNA and this is consistent with the cleavage results that indicate localized rather than widespread changes in cleavage. The cleavage results with TmPyP4 are also depicted in Figure 3. The cleavage pattern indicates that TmPyP4 binds to multiple sites of the DNA as changes in cleavage are observed for most of the residues. The changes in the extent of cleavage as a function of TmPyP4 concentration indicate that the binding constants of these sites are similar. At TmPyP4 concentrations above about 10 mM there are very large changes in cleavage. An investigation of the TmPyP4 binding to a human telomeric quadruplex found that there were up to four binding sites per quadruplex. The results on TmPyP4 binding to TBA also indicate multiple binding sites. These cleavage results indicate that NSC 176319 and NMM each have a preferential binding site while NSC 91881 and TmPyP4 bind to multiple sites. The effect of NMM appears to be primarily on a single residue and there are many ways that the NMM complex could form leading to a selective effect on this single residue. NSC 176319 appears to alter the cleavage at four residues that are spatially close together in the TT loops of the chair structure. PMCA has contributed to a number of important perspectives in prion biology, however, its conventional application to certain investigations still faces a few challenging problems. One of these problems is associated with the source of PMCA substrate. PMCA was originally designed to use brain homogenate derived from healthy animals that contains an excess amount of PrPC, to which a minute amount of prion-infected brain material, the source of PrPSc, was diluted.