Crp peptides in cancer

1. The role of cell-
penetrating peptides in
potential anti-cancer
therapy

2. The role of cell-penetrating
peptides in potential anti-cancer
therapy
• Name. Iqra Yaseen
• Roll no. BS-BSE-19-35
• Session. 2019-2023
• Course Title Structural Biology
• Course code BCH-482
• Assignment Submitted to:
• Dr. Batool Fatima
• Bagauddin Zakaria University Multan

3. Cell Penetrating
Peptides:
• Cell-penetrating peptides (CPPs) are typically
made up of 5–30 amino acids, and can be utilised
as molecular transporters to facilitate the
passage of therapeutic drugs across physiological
barriers.
• Targeting polypeptides, the protein transduction
domain (PTD), and trojan horse peptides,1
• Derived from natural or non-natural proteins or
chimeric sequences, crossing the cell membrane,
delivering various compounds, such as small
molecules, nuclear acids, proteins, viruses,
imaging agents and drugs,2,3 carrying them into
cells in the process
• Enhance or inhibit certain specific pathways of
intracellular signal transduction.
• Used in many anti-cancer treatment strategies,
serving as an excellent potential choice for
oncology treatment.

4. THE UPTAKE MECHANISM OF
CPPs:
• Mechanisms of the intracellular entry of CPPs.
• The involved pathways can be divided into two groups:
endocytosis (blue) and energy-independent mechanisms
(pink).
• Endocytosis pathways consist of macropinocytosis,
caveolin-mediated endocytosis, clathrin-mediated
endocytosis and clathrin and caveolin-independent
endocytosis.
• Energy-independent mechanisms have been proposed to
occur through: the ‘barrel-stave’ model, the ‘carpet-like’
model, the inverted micelle model, the membrane thinning
mode and another hypothesis of ‘membrane thinning’.
• The small molecules involved in the uptake progress have
been marked in the domain of the relevant pathway

5. Schematic representation of
mechanisms for CPPs internalisation

6. Intrinsic anticancer peptides

7. Mechanisms to enhance the
specialty of CPPs.
• (A) The polycation active domain is cationic
and the shielding domain is anionic. The
cleavable linking arm is the key to specificity.
• (B) The cationic peptide allows selective entry
of the cargoes into cells.
• (C) The combination of CPPs with the
antibody has been proved to improve the
specificity.
• (D) Works by targeting receptors or ligands.
• (E) EPR refers to the enhanced permeability
and retention effect. Passive targeting based
on EPR can be utilised to improve the

8. Mechanisms to enhance the
specialty of CPPs.

9. The activation and cellular
uptake of ACPPs
• ACPPs are a new type of carrier that can be activated by special
enzymes in the tumour tissue site to induce cell penetration.
• The molecular structure generally includes three functional regions:
1. polycation active domain with the cell-penetrating ability (e.g.
CPPs);
2. a cleavable connecting arm;
3. polyanion shielding domain.
• There is the high-expressed protease at the tumour site.
• Certain internal environmental factors such as low pH, and external
physicochemical stimulation such as light and exogenous substances
are the conditions that can dependently trigger cleavage between
polycation active domain and polyanion shielding domain.
• This schematic diagram selects the most potential protease MMP2/9
as a shear to activate the activatable CPP compound. After cleavage
in specific sites, they can enter tumour cells by uptake
mechanisms.

10. The activation and cellular
uptake of ACPPs.

11. Tumour Homing Peptides

12. Mechanisms of CPP act in
immunotherapy
• Circulating iRGD-modified T cells are tethered and rolled in blood
flow by the engagement of αvβ3/αvβ5 expressed on tumour vascular
endothelial cells.
• There are three CPP complexes:
• (i) IRGD (Lowest curative effect);
• (ii) iRGD-anti-CD3 (Medium curative effect)
• (iii) iRGD-anti-CD3 combine with PD-1. (Best curative effect)
• The key to facilitating tumour infiltration is to promote the opening
of cell connections. There are two main mechanisms:
• (A) The interaction also initiates the proteolysis of iRGD and expose
the CendR motif.
• The truncated peptide then binds to NRP-1, triggering the tyrosine
phosphorylation of VE-cadherin and the formation of intercellular
gaps.
• (B) Another vesicular transport pathway in the endothelial cytoplasm
is termed vesiculovacuolar organelles. Then, the connected
lymphocytes cross the vessel wall and infiltrate into the tumour
parenchyma

13. Mechanisms of CPP act in
immunotherapy