Structural requirements of heparin-like molecules for invasion-inhibitory activity. A panel of modified heparins and K5 polysaccharides was tested for inhibition of invasion. (A) Growth-inhibitory activity of selectively desulfated heparins against P falciparum blood stage parasites. (B) Growth-inhibitory activity of K5 polysaccharide derivatives with low (K5-OS-L) and high (K5-OS-H) levels of O-sulfation. (C) Inhibitory activity of K5 polysaccharides with low (K5-NSOS-L) and high (K5-NSOS-H) levels of N- and O-sulfation, compared with the same molecules that have GlcA partially epimerized to IdoA (EK5; ratio of GlcA/IdoA is 50:50). (D) The degree of sulfation (d.o.s.; number of sulfate groups per disaccharide unit) of heparin and heparin-like molecules was compared with the IC₅₀ (μg/mL). A DOS more than or equal to 2 (dashed line) was required for inhibitory activity. Noninhibitory molecules were plotted as having an IC₅₀ of 500 μg/mL. Calculated IC₅₀ values for all molecules are shown in Table 1. (E) Inhibitory activity of heparin and CSC oligosaccharides of different chain lengths (2-16 monosaccharide units), tested at 100 μg/mL. Data are mean growth ± SEM (3 assays in duplicate).