An ongoing collaboration with David Craik, Institute of Molecular Bioscience, University of Queensland involves a family of antiviral plant peptides (cyclotides) that have a cyclic amino acid backbone. These 30-35 amino acid peptides have potent anti-HIV properties and we are studying the structural features associated with their activity against HIV. The Craik laboratory has developed synthetic methods to produce cyclotides with specific alanine substitutions. These peptidess are analyzed by NMR to assure they adopt a native fold and then tested by MTDP for cytotoxic properties and their ability to inhibit HIV. We have established a few critical residues required for anti-HIV activity and hope to optimize this activity while reducing the undesirable cytotoxic properties of the modified cyclotides.