Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jul 28;23(15):8322.
doi: 10.3390/ijms23158322.

A Second Life for MAP, a Model Amphipathic Peptide

Affiliations
Review

A Second Life for MAP, a Model Amphipathic Peptide

Sara Silva et al. Int J Mol Sci. .

Abstract

Cell-penetrating peptides (CPP) have been shown to be efficient in the transport of cargoes into the cells, namely siRNA and DNA, proteins and peptides, and in some cases, small therapeutics. These peptides have emerged as a solution to increase drug concentrations in different tissues and various cell types, therefore having a relevant therapeutic relevance which led to clinical trials. One of them, MAP, is a model amphipathic peptide with an α-helical conformation and both hydrophilic and hydrophobic residues in opposite sides of the helix. It is composed of a mixture of alanines, leucines, and lysines (KLALKLALKALKAALKLA). The CPP MAP has the ability to translocate oligonucleotides, peptides and small proteins. However, taking advantage of its unique properties, in recent years innovative concepts were developed, such as in silico studies of modelling with receptors, coupling and repurposing drugs in the central nervous system and oncology, or involving the construction of dual-drug delivery systems using nanoparticles. In addition to designs of MAP-linked vehicles and strategies to achieve highly effective yet less toxic chemotherapy, this review will be focused on unique molecular structure and how it determines its cellular activity, and also intends to address the most recent and frankly motivating issues for the future.

Keywords: CNS; cell-penetrating peptides; delivery system; drug repurposing; model amphipathic peptide; nanoparticles; oncology.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the different types of peptides available and their different activities. In-depth representation of cell-penetrating peptides as delivery molecules and potential other interactions.
Figure 2
Figure 2
Different representations of peptide MAPs. (A)—Structure sequence of MAP (ChemDraw 19.0); (B)—Three-dimensional representation of MAP sequence (ChemBio 3D ultra); (C)—Secondary structure (in carton) and an H2O mesh surface of MAP (3D data retrieved from CPP database (CPPsite 2.0) and analyzed by ChemBio 3D ultra); (D)—Projection wheel of MAP (hydrophobic part is blue-shaded and charged residues are highlighted with rectangles).
Figure 3
Figure 3
(A)—Slab-view interaction with UR-MK299, MAP and NPY against NPY1R obtained by molecular docking with information obtained by X-ray diffraction. (B)—Representation of the volume occupied by UR-MK299, MAP and NPY when complexed with NPYR1 (Reproduced and edited from [71], MDPI, 2022).

Similar articles

Cited by

References

    1. Lindgren M., Langel Ü. Methods in Molecular Biology (Clifton, N.J.) Volume 683. Humana Press; Totowa, NJ, USA: 2011. Classes and Prediction of Cell-Penetrating Peptides; pp. 3–19. - PubMed
    1. Frankel A.D., Pabo C.O., Frankel A.D., Pabo C.O. Cellular uptake of the tat protein from human immunodeficiency virus. Cell. 1988;55:1189–1193. doi: 10.1016/0092-8674(88)90263-2. - DOI - PubMed
    1. Vivès E., Brodin P., Lebleu B. A truncated HIV-1 Tat protein basic domain rapidly translocates through the plasma membrane and accumulates in the cell nucleus. J. Biol. Chem. 1997;272:16010–16017. doi: 10.1074/jbc.272.25.16010. - DOI - PubMed
    1. Xie J., Bi Y., Zhang H., Dong S., Teng L., Lee R.J., Yang Z. Cell-Penetrating Peptides in Diagnosis and Treatment of Human Diseases: From Preclinical Research to Clinical Application. Front. Pharmacol. 2020;11:697. doi: 10.3389/fphar.2020.00697. - DOI - PMC - PubMed
    1. Borrelli A., Tornesello A.L., Tornesello M.L., Buonaguro F.M. Cell penetrating peptides as molecular carriers for anti-cancer agents. Molecules. 2018;23:295. doi: 10.3390/molecules23020295. - DOI - PMC - PubMed

MeSH terms

LinkOut - more resources