CV-N is an 11 kDa, anti-HIV protein that binds strongly to the envelope glycoprotein, gp120, expressed on the outer surface of the free virion and also on HIV-infected cells. As such, it represents an important lead for development of anti-HIV therapeutics. Marine toxins such as the halichondrins have potent in vivo cytotoxicities and are lethal to cells. The combination of this potency of the marine toxins with the unique targeting capability of CV-N has been harnessed to produce conjugates that have the potential to selectively target and eliminate HIV-infected cells. Three forms of the protein were developed; the native protein itself, a derivative recombinantly produced in E. coli with an extra cysteine at the C-terminal (CV-N-Cys) and CV-N with the lysine side chain amines converted into thiols (thiolated-CV-N). To facilitate release of the toxin within infected cells an enzymatically-cleavable pHdependent biolinker was incorporated separating the toxin from the protein. The chemistry required for incorporation of protein, biolinker, and toxin, was established through synthesis of fluorescently labelled conjugates capable of reaction with CV-N. Biological testing of these derivatives showed no interference with the anti-HIV activity of the CV-N when conjugated in these model compounds. Synthetic strategies were developed to produce two derivatives of norhomohalichondrin B amine, both containing the cleavable biolinker, but with activation from succinimidyl esters and maleimido groups respectively. Native CV-N was reacted with the succinimidyl ester derived toxin construct to produce a CV-N-biolinker-toxin conjugate. The maleimido derivative toxin construct was reacted with both CV-N-Cys and thiolated-CV -N to produce closely related CV-N-toxin conjugates. Investigations into the binding properties and cell toxicities of these conjugates is currently underway.