Design and synthesis of small semi-mimetic peptides with immunomodulatory activity based on myelin basic protein (MBP).
Experimental allergic encephalomyelitis (EAE) is induced in susceptible animals by immunodominant determinants of myelin basic protein (MBP). Analogs of these disease-associated peptides have been identified with disease progression upon coimmunization. Usage of peptides, with disease-specific immunomodulatory capacity in vivo is limited, however, due to their sensitivity to proteolytic enzymes. Alternative approaches include the development of mimetic molecules which maintain the biological function of an original peptide, yet are stable and able to elicit their response in pharmacological quantities. A novel technique was employed to design a series of semi-mimetic peptides, based on the guinea pig MBP72-85 peptide used to induce EAE in Lewis rats. We used isonipecotic (iNip) and aminocaproic (Acp) acids as templates. Acp-MBP72-85 peptide derived analogues were effective in inducing EAE compared to iNip-peptide analogues which were ineffective at 350 micrograms. These findings suggest that the design and synthesis of semi-mimetic peptide molecules with immunomodulatory potential is possible and that eventually these molecules may form the basis for the development of novel and more effective disease-specific therapeutic agents.
Tselios
T
T
Department of Chemistry, University of Patras, Hellas.
Probert
L
L
Kollias
G
G
Matsoukas
E
E
Roumelioti
P
P
Alexopoulos
K
K
Moore
G J
GJ
Matsoukas
J
J
D000595:Amino Acid Sequence; D000614:Aminocaproates / Q000737:chemistry*; D000818:Animals; D015195:Drug Design; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D007540:Isonipecotic Acids / Q000737:chemistry*; D008956:Models, Chemical; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis*; D011487:Protein Conformation; D051381:Rats; D011917:Rats, Inbred Lew; D013698:Templates, Genetic
D000614:Aminocaproates; D007540:Isonipecotic Acids; D004676:Myelin Basic Protein; D010455:Peptides