Linear Peptides in Intracellular Applications

Title:Linear Peptides in Intracellular Applications

Volume: 24 Issue: 17

Author(s): Cristiane R. Zuconelli, Roland Brock*Merel J.W. Adjobo-Hermans

Affiliation:

• Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen Medical Center, PO Box 9101, 6500 HB Nijmegen,Netherlands

Keywords: Synthetic peptides, intracellular peptides, bioactive endogenous peptides, peptide stability, intracellular signaling, peptide delivery.

Abstract: To this point, efforts to develop therapeutic peptides for intracellular applications were guided by the perception that unmodified linear peptides are highly unstable and therefore structural modifications are required to reduce proteolytic breakdown. Largely, this concept is a consequence of the fact that most research on intracellular peptides hitherto has focused on peptide degradation in the context of antigen processing, rather than on peptide stability. Interestingly, inside cells, endogenous peptides lacking any chemical modifications to enhance stability escape degradation to the point that they may even modulate intracellular signaling pathways. In addition, many unmodified synthetic peptides designed to interfere with intracellular signaling, following introduction into cells, have the expected activity demonstrating that biologically relevant concentrations can be reached. This review provides an overview of results and techniques relating to the exploration and application of linear, unmodified peptides. After an introduction to intracellular peptide turnover, the review mentions examples for synthetic peptides as modulators of intracellular signaling, introduces endogenous peptides with bioactivity, techniques to measure peptide stability, and peptide delivery. Future experiments should elucidate the rules needed to predict promising peptide candidates.

Cite this article as:

Zuconelli R. Cristiane, Brock Roland*, Adjobo-Hermans J.W. Merel , Linear Peptides in Intracellular Applications, Current Medicinal Chemistry 2017; 24 (17) . https://dx.doi.org/10.2174/0929867324666170508143523