Combinatorial discovery of tumor targeting peptides using phage display.
Peptides possess appropriate pharmacokinetic properties to serve as cancer imaging or therapeutic targeting agents. Currently, only a small number of rationally-derived, labeled peptide analogues that target only a limited subset of antigens are available. Thus, finding new cancer targeting peptides is a central goal in the field of molecular targeting. Novel tumor-avid peptides can be efficiently identified via affinity selections using complex random peptide libraries containing millions of peptides that are displayed on bacteriophage. In vitro and in situ affinity selections may be used to identify peptides with high affinity for the target antigen in vitro. Unfortunately, it has been found that peptides selected in vitro or in situ may not effectively target tumors in vivo due to poor peptide stability and other problems. To improve in vivo targeting, methodological combinatorial chemistry innovations allow selections to be conducted in the environment of the whole animal. Thus, new targeting peptides with optimal in vivo properties can be selected in vivo in tumor-bearing animals. In vivo selections have been proven successful in identifying peptides that target the vasculature of specific organs. In addition, in vivo selections have identified peptides that bind specifically to the surface of or are internalized into tumor cells. In the future, direct selection of peptides for cancer imaging may be expedited using genetically engineered bacteriophage libraries that encode peptides with intrinsic radiometal-chelation or fluorescent sequences.
Landon
Linda A
LA
Department of Biochemistry, M743 Medical Sciences Building, University of Missouri, Columbia, Missouri 65212, USA.
Deutscher
Susan L
SL
D000595:Amino Acid Sequence; D000818:Animals; D020650:Combinatorial Chemistry Techniques; D003952:Diagnostic Imaging; D016503:Drug Delivery Systems; D051379:Mice; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D019151:Peptide Library; D010455:Peptides / Q000627:therapeutic use*; D011956:Receptors, Cell Surface / Q000378:metabolism; D014407:Tumor Cells, Cultured
D019151:Peptide Library; D010455:Peptides; D011956:Receptors, Cell Surface