Compared to 2×2 GG/GG internal loops, 2×2 CC/CC internal loops, which can be observed in antisense r(C4G2) exp strand, are not very dynamic. A recent structural study displayed that tandem C/C mismatches prefer all-anti orientations , which is in line with previous observations that pyrimidines are mostly observed in anti states . Nevertheless, circular dichroism (CD) and differential scanning calorimetry (DSC) studies on r(CCCCGG)n, where n was varied from 2 to 10, suggest also the existence of alternative structures , an indication that 2×2 CC/CC loops are not as rigid as suggested by X-ray studies. Because antisense RNA foci have been also observed in abundance in neurons of the frontal cortex , they can be exploited by small molecules targeting the 2×2 CC/CC loop motifs.