We found that CPPÀPMOF conjugates containing X/B residues did not enter cells as efficiently as R 8 À and R 9 ÀPMO conjugates. This is consistent with our previous finding for the (RXR) 4 conjugate (6). We have found that cell surface proteoglycans were involved with binding of the TatÀ, R 9 F 2 À and (RXR) 4 ÀPMO conjugates with the (RXR) 4 conjugate having the lowest binding affinity. Insertion of X into an oligoarginine CPP reduces the charge density and may lead to decreased binding affinity for proteoglycans. Despite the lower cellular uptake of X/B-containing CPP-PMO, they generated higher antisense activities in the cell nucleus than oligoarginineÀPMO. We have found that endocytosis was the internalization mechanism (at least primarily) for oligoarginine-and (RXR) 4 ÀPMO conjugates. Indication of different uptake mechanisms was not found among these conjugates (6) . Therefore we hypothesize that X/B-containing conjugates have a greater ability to escape from endosomes/lysosomes than oligoarginine conjugates by a mechanism as yet to be studied.