The role of the cyclic peptide backbone in the anti-HIV activity of the cyclotide kalata B1.

The plant cyclotides, the largest known family of circular proteins, have tightly folded structures and a range of biological activities that lend themselves to potential pharmaceutical and agricultural applications. Based on sequence homology, they are classified into the bracelet and Möbius subfamilies. The bracelet subfamily has previously been shown to display anti-HIV activity. We show here that a member of the Möbius subfamily, kalata B1, also exhibits anti-HIV activity despite extensive sequence differences between the subfamilies. In addition, acyclic permutants of kalata B1 displayed no anti-HIV activity, suggesting that this activity is critically dependent on an intact circular backbone.