Mechanism of RNA cleavage catalyzed by sequence specific polyamide nucleic acid-neamine conjugate

作者：Chaubey Binay; Tripathi Snehlata; Desire Jerome; Baussanne Isabelle; Decout Jean Luc; Pandey Virendra N^*

来源：Oligonucleotides, 2007, 17(3): 302-313.

DOI：10.1089/oli.2007.0085

In earlier studies, we found that a conjugate of neamine-polyamide nucleic acid targeting transactivation response element of HIV-1 RNA genome ( HIV- 1 TAR) displayed anti- HIV-1 activity and sequencespecific cleavage of the target RNA in vitro. Here we show that both the position of conjugation of polyamide nucleic acid ( PNA) on neamine and the length of the spacer are critical parameters for conferring cleavage activity to the conjugate. The conjugation of PNA via a spacer incorporating 11 atoms to the 5- position of ring I of the neamine core conferred sequence- specific RNA cleavage activity on the conjugate, while conjugation to the 4'- position of ring II abolished this activity. Similarly, 5- neamine PNA complementary to TAR sequence of HIV-1 genome (PNA(TAR)) conjugates having either a 23-atom spacer or a bulky dansyl group between PNA and the neamine core also resulted in complete loss of cleavage activity. Based on these observations, we propose a mechanism for the observed RNA cleavage catalyzed by the conjugate involving unprotonated and protonated amino groups at the 3-position of ring I and the 6'- position of ring II of the neamine core, respectively.

• 出版日期2007-9