SIMULTANEOUS SYNTHESIS OF PEPTIDE LIBRARIES ON SINGLE RESIN AND CONTINUOUS CELLULOSE MEMBRANE SUPPORTS - EXAMPLES FOR THE IDENTIFICATION OFPROTEIN, METAL AND DNA-BINDING PEPTIDE MIXTURES

Peptide libraries were simultaneously synthesized on single supports b y double coupling 0.8 equivalents of an equimolar acylating amino acid mixture consisting of 19 amino acids (cysteine omitted) at randomized sites, thus compensating for the different coupling rates of the amin o acids. Peptide epitope mixtures, as well as very complex mixtures su ch as a completely randomized hexapeptide, were prepared and analyzed by HPLC and amino acid analysis. The results obtained indicate that th is method can be applied to the synthesis of peptide libraries. Parts of a simultaneously synthesized solution phase combinatorial library X XB(1)B(2)XX were successfully used for the detection of the linear epi tope HFND of transforming growth factor-alpha (TGF alpha) recognized b y the monoclonal antibody Tab2. Furthermore, novel combinatorial pepti de libraries XXB(1)B(2)XX were prepared on continuous cellulose membra ne supports, also allowing the identification of TGF alpha epitope seq uences. In addition, peptide mixtures that bound to a double-stranded DNA (15mer) and silver were identified. These preliminary results indi cate that cellulose-bound combinatorial peptide libraries can be used for the rapid and inexpensive screening of millions of peptides to ide ntify single molecules that bind any given ligand such as proteins, nu cleic acids and metals.