Immunogen, conformation

In the rare case when a peptide showing some promise has been identified, further immunization trials are necessary to establish its value as a practical synthetic vaccine. Since peptides are usually poor immunogens and do not mimic well the conformation of the corresponding antigenic site in the... 

Because conformational epitopes are not easily mimicked with linear peptides, which can elicit nonspecific antibodies, several alternative strategies such as synthetic cyclic peptides have been developed [see e.g., (18)]. A similar conformational restriction was seemingly achieved with a P-amyloid peptide that was anchored to the surface of liposomes via hydrophobic tails introduced at its both N- and C-termini. The reconstituted peptide proved highly immunogenic and elicited antibodies that could significantly prevent amyloid plaque formation in a model system (70). 

The weakly immunogenic protamine sulfate USP (1) condenses DNA to form a toroid structure of super-coiled DNA about 50 nm in diameter (2). The DNA in this form or in the preformed LPDI complex cannot be displaced from the protamine by polycations such as spermidine and histones or by other nucleic acids like genomic DNA (2). DNA in this toroid structure is transcriptionally inactive and this conformation allows for protection of DNA from enzymatic degradation by nucleases and other environmental assaults such as mechanical stress (1,2). After the liposome surrounds the toroid, the resulting homogenous LPDI nanoparticles are slightly less than... 

In preparation for use as a surrogate vaccine, these peptides were synthesized as conjugates to tetanus toxoid, and in this form also competed with the 0-antigen polysaccharide for binding [104]. Whether these peptides will function as effective immunogenic mimics will likely depend on their propensity to adopt the bioactive conformation in solution. A certain amount... 

Spiro lactam 15 (Scheme 9), a dipeptide mimic with C (/)<-+Na(/ + l) cyclization, was used to replace the Pro-Tyr segment of an immunogenic peptide. 69 Comprehensive conformational analysis led to the conclusion that a type-II p-turn conformation was adopted in solution. 

Elofsson M, Roy S, Walse B, Kihlberg J, Solid-phase synthesis and conformational studies of glycosylated derivatives of helper-T-cell immunogenic peptides from hen-egg lysozyme., Carbohydr. Res., 17, 246 89-103, 1993. 

Antibodies of this type are formed if the synthetic peptide used as the immunogen is the same as a segment of a protein (antibody) that lies on the surface in its native form, and whose native conformation can in part be adopted by the peptide (antigen). 

---