Cross-blocking assay to define the spatial relationship between linear and cyclic peptide contact sites. Different concentrations of Rp1-L (♦), Rp5-L (▴), RpCD20-L (▪), and Rp15-C (○) were mixed with an appropriate dilution of purified rituximab (3 μg/mL). After 1-hour incubation at 4°C, the mixture was added to wells of a 96-well microtiter plate previously sensitized with peptide Rp1-L (A), Rp5-L (B), Rp15-C (C), and RpCD20-L (D). Rituximab binding to peptide was then detected with HRP-conjugated xeno-antibodies to human IgG (Fc portion). Binding of rituximab to peptide in the presence of homologous peptide (broken line) and of Qp1a peptide (×) were included as positive and negative controls, respectively. Results are expressed as percentage of binding compared with binding in the absence of inhibitor.