Synthetic peptide vaccine design: synthesis and properties of a high-density multiple antigenic peptide system.

Abstract

A convenient and versatile approach to the direct synthesis of a peptide-antigen matrix by the solid-phase method is described. The approach is called the multiple antigen peptide system (MAP) and it utilizes a simple scaffolding of a low number of sequential levels (n) of a trifunctional amino acid as the core matrix and 2n peptide antigens to form a macromolecule with a high density of peptide antigens of final Mr 10,000. The MAP model chosen for study was an octa-branching MAP consisting of a core matrix made up of three levels of lysine and eight amino terminals for anchoring peptide antigens. The MAP, containing both the core matrix and peptides of 9-16 amino acids, was prepared in a single synthesis by the solid-phase method. Six different MAPs elicited specific antibodies in rabbits and mice, of which five produced antibodies that reacted with their corresponding native proteins. In rabbits, the sera had a considerably higher titer of antibodies than sera prepared from the same peptides anchored covalently to keyhole limpet hemocyanin as carrier. Thus, the MAP provided a general, but chemically unambiguous, approach for the preparation of carrier-bound antigens of predetermined and reproducible structure and might be suitable for generating vaccines.

Deiminated Epstein‐Barr virus nuclear antigen 1 is a target of anti–citrullinated protein antibodies in rheumatoid arthritis

“…Synthetic peptides were obtained by solid-phase synthesis using 9-fluorenylmethoxycarbonylprotected amino acids, according to the method described by Merrifield (22) and modified by Atherton and Sheppard (23), in the form of linear peptides or as multiple antigen peptides (MAPs) bearing 4 identical sequences on a lysine scaffold (24). The sequences are shown in Table 1.…”

Dendritic supports in organic synthesis

“…thesis Tam, 1988 , this approach was basically developed by Bradley and co-workers. In one of their first reports on this issue, PAMAM dendrons were synthesized onto an insoluble Ž .…”

GCAP‐II: Isolation and characterization of the circulating form of human uroguanylin

“…A multiple antigenic peptide (MAP) consisting of a branched heptalysine core with eight copies of the N-terminal domain of GCAP-II (FKTLRTIANDD) covalently bound was synthesized [12,14]. Antisera were raised in rabbits and used to localize the peptide in various tissues such as colon, liver, kidney, and stomach.…”