Synthesis and application of peptide dendrimers as protein mimetics.
The use of peptides to mimic a portion of a protein structure is a challenging and powerful tool in the discovery of new drugs. In native proteins, discontinuous bioactive peptide surfaces are held together in a particular conformation by the structural rigidity of the protein. Approaches to mimicking a structural surface center on bringing the potential peptide sequences together by assembling the peptide chains on a template. These templates can be flexible dendrimeric or cyclic peptides as well as more rigid organic molecules. The Multiple Antigen Peptide (MAP) system represents a novel approach to preparing peptide immunogens. The MAP consists of an inner core matrix built up of a large layer of Lys residues and a surface of peptide chains attached to the core matrix. Because of its dendrimeric structure, MAP can be very useful as a template for assembling potential peptide surfaces. A variation of this procedure, the cyclic Multiple Antigen Peptide (cMAP) approach, is also presented here. Having branched multiple closed-chain architectures, the cMAP system is often a superior approach for protein mimetics because the multiple constrained peptides can mimic bioactive conformations. Whether to select this approach over MAP depends on the properties of the peptides, but usually if the peptides are too small to adopt a stable conformation on their own, incorporation of a cyclic structure may be necessary. MAPs have been applied to areas of study such as inhibitors, artificial proteins, affinity purifications, and intracellular transport.
Tam
J P
JP
Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Spetzler
J C
JC
D032701:Biomimetics / Q000379:methods; D050091:Dendrimers / Q000138:chemical synthesis* / Q000737:chemistry; D008956:Models, Chemical; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D011506:Proteins / Q000138:chemical synthesis* / Q000737:chemistry
D050091:Dendrimers; D010455:Peptides; D011506:Proteins