SCREENING OF RANDOM PEPTIDE PHAGE DISPLAY LIBRARIES WITH ANTICARDIOLIPIN ANTIBODIES.

Edward J. Victoria, Michael J. Branks, Patricia C. Hammes, Merle S. Hayag, David M. Marquis and Michael K. Pabarcus.

La Jolla Pharmaceutical Company, San Diego, CA 92121

Autoimmune anticardiolipin antibodies (aPL) have been implicated in ischemic stroke, recurrent fetal loss, and thrombocytopenia. We have generated linear and cyclized random peptide libraries of variable lengths on the pIII protein of fd phage. The combined libraries were screened for mimetic epitopes with several aPL which were affinity-purified with cardiolipin-containing liposomes and chromatography. Very high-titer aPL (>100 GPL) were required. An experimental design of gradually increasing stringency for the selection of candidate phage led to synthetic peptide sequences which immunospecifically bound aPL. Several aPL selected cys-flanked 7-mer sequences in preference to ten other component libraries available in the pool.

Presented at the Western Biotech Conference, Oct. 18-21, 1995, San Diego, CA.