Synthesis and Characterization of Immunoglobulin Variable Region Heavy and Light Chain Fragments,

These syntheses of V sub L1-63 and V sub H1-68 of murine myeloma McPc603 represent the first automated stepwise syntheses of an antigen-binding variable region. A previous synthesis of V sub H16-68 was performed via fragment condensation. Stepwise synthesis of the V sub L region of another antibody, MOPX 315, gave a small amount of binding activity. The F sub H1-68 and V sub L1-63 fragments targeted in this synthesis each contain two out of the three hypervariable loops thought to be responsible for the specificity of the antibody. Anticipated synthetic problems arose from the length of the proteins 68 and 63 amino acids and the extreme hydrophobicity and basicity of the products. The stepwise strategy avoids problems of solubility and purification encountered in the fragment approach.