Chemoselective approaches to the preparation of peptide dendrimers and branched artificial proteins using unprotected peptides as building blocks
Tam, J.P.; Spetzler, J.C.
Biomedical Peptides Proteins and Nucleic Acids Structure Synthesis and Biological Activity 1(3): 123-132
1995
ISSN/ISBN: 1353-8616 PMID: 9346843 Document Number: 441650
Peptide dendrimers such as Multiple Antigen Peptides (MAPs) are artificial proteins with branched architectures. They hold promise in biochemical and biomedical applications such as synthetic vaccines, serodiagnostics and intracellular delivery of peptides. We have shown that a new design of MAPs containing lipidated built-in adjuvant can be delivered by oral administration to elicit systemic and mucosal immunoglobulins as well as cytotoxic T-lymphocytes. For synthetic vaccines, it is desirable to obtain highly homogeneous preparations. To provide the precision and chemical unambiguity of this class of artificial proteins, we have devised several chemoselective approaches by thiol and carbonyl chemistries to facilitate their synthesis using unprotected peptide segments as building blocks and ligating them to the core matrix. This paper describes the methods of preparation, comparative studies of stability, and presents results of the preparation of antigens containing preformed multiple disulfides.