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{"id":1102,"date":"2025-05-15T01:51:59","date_gmt":"2025-05-15T06:51:59","guid":{"rendered":"https:\/\/www.creative-peptides.com\/blog\/?p=1102"},"modified":"2025-05-15T01:54:50","modified_gmt":"2025-05-15T06:54:50","slug":"cell-penetrating-peptides-cpps-used-in-drug-delivery-systems","status":"publish","type":"post","link":"https:\/\/www.creative-peptides.com\/blog\/cell-penetrating-peptides-cpps-used-in-drug-delivery-systems\/","title":{"rendered":"Cell-penetrating Peptides (CPPs) Used in Drug Delivery Systems"},"content":{"rendered":"\n

The cell membrane is a natural barrier composed of a lipid bilayer, which restricts the entry of external substances into the cell and ensures the stability of the intracellular environment. At the same time, to maintain a stable internal environment, the human body possesses various physiological barriers, such as the blood-brain barrier (BBB), blood-retinal barrier, and placental barrier. One of the main obstacles to drug delivery is the inability of drugs to penetrate the cell membrane and physiological barriers, thereby preventing them from exerting their therapeutic effects inside the cell.<\/p>\n\n\n\n

Cell-penetrating peptides (CPPs)<\/a> are short peptides capable of entering cells without disrupting membrane integrity. They typically consist of 5 to 30 amino acids<\/a> and are rich in basic amino acids, including arginine and lysine. Under physiological conditions, CPPs share two common characteristics: a positive charge and amphiphilicity. In recent years, CPPs have been widely applied in drug delivery systems.<\/p>\n\n\n\n

The recognized mechanisms by which CPPs penetrate cell membranes fall into two categories: endocytosis and direct translocation. Endocytosis is an energy-dependent process and includes three main pathways: macropinocytosis, caveolae-mediated endocytosis (CvME), and clathrin-mediated endocytosis (CME). In contrast, direct translocation is an energy-independent process facilitated by electrostatic interactions between the positively charged CPPs and the negatively charged membrane components and phospholipid bilayer, promoting direct membrane permeation. Several models have been proposed for direct penetration, including the barrel-stave model, carpet model, toroidal pore model, and inverted micelle model.<\/p>\n\n\n\n

A summary of the cell-penetrating peptide used in drug delivery is as follows:<\/p>\n\n\n\n

1. Polyarginine<\/strong><\/strong><\/h2>\n\n\n\n

Single-letter code: H2N-RRRRRRRRR-OH<\/p>\n\n\n\n

Three-letter code: H2N-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-OH<\/p>\n\n\n\n

Number of amino acids: 9<\/p>\n\n\n\n

Molecular formula: C54H110N36O10<\/p>\n\n\n\n

Average molecular weight (MW): 1423.69<\/p>\n\n\n\n

2. Transportan 10 (TP10)<\/strong><\/strong><\/h2>\n\n\n\n

Single-letter code: H2N-AGYLLGKINLKALAALAKKIL-OH<\/p>\n\n\n\n

Three-letter code: H2N-Ala-Gly-Tyr-Leu-Leu-Gly-Lys-Ile-Asn-Leu-Lys-Ala-Leu-Ala-Ala-Leu-Ala-Lys-Lys-Ile-Leu-OH<\/p>\n\n\n\n

Number of amino acids: 21<\/p>\n\n\n\n

Molecular formula: C104H184N26O24<\/p>\n\n\n\n

Average molecular weight (MW): 2182.73<\/p>\n\n\n\n

3. Tumor-Lineage Homing CPP<\/strong><\/strong><\/h2>\n\n\n\n

Single-letter code: H2N-RLYMRYYSPTTRRYG-OH<\/p>\n\n\n\n

Three-letter code: H2N-Arg-Leu-Tyr-Met-Arg-Tyr-Tyr-Ser-Pro-Thr-Thr-Arg-Arg-Tyr-Gly-OH<\/p>\n\n\n\n

Number of amino acids: 15<\/p>\n\n\n\n

Molecular formula: C89H135N27O23S1<\/p>\n\n\n\n

Average molecular weight (MW): 1983.26<\/p>\n\n\n\n

4. dNP2<\/strong><\/strong><\/h2>\n\n\n\n

Single-letter code: H2N-CKIKKVKKKGRKKIKKVKKKGRK-OH<\/p>\n\n\n\n

Three-letter code: H2N-Cys-Lys-Ile-Lys-Lys-Val-Lys-Lys-Lys-Gly-Arg-Lys-Lys-Ile-Lys-Lys-Val-Lys-Lys-Lys-Gly-Arg-Lys-OH<\/p>\n\n\n\n

Number of amino acids: 23<\/p>\n\n\n\n

Molecular formula: C125H245N43O24S1<\/p>\n\n\n\n

Average molecular weight (MW): 2766.62<\/p>\n\n\n\n

5. RVRR<\/strong><\/strong><\/h2>\n\n\n\n

Single-letter code: H2N-RVRR-OH<\/p>\n\n\n\n

Three-letter code: H2N-Arg-Val-Arg-Arg-OH<\/p>\n\n\n\n

Number of amino acids: 4<\/p>\n\n\n\n

Molecular formula: C23H47N13O5<\/p>\n\n\n\n

Average molecular weight (MW): 585.70<\/p>\n\n\n\n

6. L-penetratin<\/strong><\/strong><\/h2>\n\n\n\n

Single-letter code: H2N-RQIKIWFQNRRMKWKK-OH<\/p>\n\n\n\n

Three-letter code: H2N-Arg-Gln-Ile-Lys-Ile-Trp-Phe-Gln-Asn-Arg-Arg-Met-Lys-Trp-Lys-Lys-OH<\/p>\n\n\n\n

Number of amino acids: 16<\/p>\n\n\n\n

Molecular formula: C104H168N34O20S1<\/p>\n\n\n\n

Average molecular weight (MW): 2246.73<\/p>\n\n\n\n

7. Activable CPP (ACPP)<\/strong><\/strong><\/h2>\n\n\n\n

Single-letter code: H2N-CRRRRRRRRGGGPKKKKKK-OH<\/p>\n\n\n\n

Three-letter code: H2N-Cys-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Gly-Gly-Gly-Pro-Lys-Lys-Lys-Lys-Lys-Lys-OH<\/p>\n\n\n\n

Number of amino acids: 19<\/p>\n\n\n\n

Molecular formula: C98H191N49O20S1<\/p>\n\n\n\n

Average molecular weight (MW): 2407.95<\/p>\n\n\n\n

8. LH2<\/strong><\/strong><\/h2>\n\n\n\n

Single-letter code: Ac-LHHLCHLLHHLCHLAG-CONH2<\/p>\n\n\n\n

Three-letter code: Ac-Leu-His-His-Leu-Cys-His-Leu-Leu-His-His-Leu-Cys-His-Leu-Ala-Gly-CONH2<\/p>\n\n\n\n

Number of amino acids: 16<\/p>\n\n\n\n

Molecular formula: C85H131O17N29S2<\/p>\n\n\n\n

Average molecular weight (MW): 1895.26<\/p>\n\n\n\n

9. Cancer Cell Line Specific CPP<\/strong><\/strong><\/h2>\n\n\n\n

Single-letter code: H2N-RLYMRYYSPTTRRYG-OH<\/p>\n\n\n\n

Three-letter code: H2N-Arg-Leu-Tyr-Met-Arg-Tyr-Tyr-Ser-Pro-Thr-Thr-Arg-Arg-Tyr-Gly-OH<\/p>\n\n\n\n

Number of amino acids: 15<\/p>\n\n\n\n

Molecular formula: C89H135N27O23S1<\/p>\n\n\n\n

Average molecular weight (MW): 1983.26<\/p>\n\n\n\n

10. T2<\/strong><\/strong><\/h2>\n\n\n\n

Single-letter code: H2N-FKKFFRKLL-OH<\/p>\n\n\n\n

Three-letter code: H2N-Phe-Lys-Lys-Phe-Phe-Arg-Lys-Leu-Leu-OH<\/p>\n\n\n\n

Number of amino acids: 9<\/p>\n\n\n\n

Molecular formula: C63H99N15O10<\/p>\n\n\n\n

Average molecular weight (MW): 1226.55<\/p>\n\n\n\n

Cell-penetrating <\/strong>P<\/strong>eptides (CPPs)<\/strong> at Creative Peptides<\/strong><\/strong><\/p>\n\n\n\n