Mimicry of protein function with cell-penetrating peptides.
Proteins are essential components of cellular processes inside cells, and their interactions between each other and with genes are important for the normal physiological functioning of cells as well as for disease states. Modulating protein interactions by different means can potentially control these interactions and restore normal function to diseased cells. The ways to do so are multiple, and such efforts often begin with knowledge of potential target proteins in order to devise mediators that retain the function of the original protein, i.e., mimic the protein functions. An alternative strategy is to utilize protein mimics to inhibit target proteins rather than restoring the activity of a protein. The vast majority of protein -mimics exploited to date have been designed to inhibit the activity of oncogenes or activate tumor suppressors for the purpose of tumor therapy. These protein mimics are usually based on small organic compounds or peptides, derived from interaction surfaces of the proteins, and in some cases, full proteins have been exploited. Although peptides and proteins are naturally highly specific and efficient inside cells, they suffer from low bioavailability resulting from their inability to enter cells. One strategy increasingly employed to facilitate the internalization of peptides and proteins has been to chemically conjugate them to cell-penetrating peptides (CPP) or to recombinantly express protein-CPP fusion constructs.This chapter provides an overview of some of the aspects of perturbing and mimicking protein interactions using peptides and proteins and CPP as transport vectors.
Department of Oncology-Pathology, Karolinska Biomics Center, Karolinska Institutet, Stockholm, Sweden. henrik.johansson@ki.se
Henrik J
HJ
Johansson
Samir E L
SE
Andaloussi
Ulo
U
Langel
D000595:Amino Acid Sequence; D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry / Q000378:metabolism*; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D021381:Protein Transport; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D025803:Tumor Suppressor Protein p14ARF / Q000737:chemistry / Q000378:metabolism
D057846:Cell-Penetrating Peptides; D011506:Proteins; D025803:Tumor Suppressor Protein p14ARF