DESIGN AND SYNTHESIS OF SMALL SEMI-MIMETIC PEPTIDES WITH IMMUNOMODULATORY ACTIVITY-BASED ON MYELIN BASIC-PROTEIN (MBP)

Experimental allergic encephalomyelitis (EAE) is induced in susceptibl e animals by immunodominant determinants of myelin basic protein (MBP) . Analogs of these disease-associated peptides have been identified wi th disease progression upon coimmunization. Usage of peptides, with di sease-specific immunomodulatory capacity in vivo is limited, however, due to their sensitivity to proteolytic enzymes. Alternative approache s include the development of mimetic molecules which maintain the biol ogical function of an original peptide, yet are stable and able to eli cit their response in pharmacological quantities. A novel technique wa s employed to design a series of semi-mimetic peptides, based on the g uinea pig MBP72-85 peptide used to induce EAE in Lewis rats. We used i sonipecotic (iNip) and aminocaproic (Acp) acids as templates. Acp-MBP7 2-85 peptide derived analogues were effective in inducing EAE compared to iNip-peptide analogues which were ineffective at 350 mu g. These f indings suggest that the design and synthesis of semi-mimetic peptide molecules with immunomodulatory potential is possible and that eventua lly these molecules may form the basis for the development of novel an d more effective disease-specific therapeutic agents.