Note for Anticancer peptide: Physicochemical property, functional aspect and trend in clinical application (Review)

Note for Anticancer peptide: Physicochemical property, functional aspect and trend in clinical application (Review)

Doi: 10.3892/ijo.2020.5099

Overview

Anticancer peptide;

• Physicochemical properties

• Amino acid composition

• Addition of chemical group

These three properties – affect

• Conformation

• Net charge

• Orientation of secondary structure

Thus, affecting specificity and ACP-cell interaction (peptide penetrating capability, stability, efficacy)

Introduction

• Anticancer peptide advantage

• High selectivity

• High penetration

• Easy modifications

• Membrane properties of cancer vs normal cells

• Membrane fluidity of cancer cells higher than healthy cells

• Contain more abundant microvilli compare with healthy cells

• Negatively charge but normal cell – neutrality

• Thus, making cancer cells more prone to ACP

• Three enzymes involved in contribution of lipid types in the cell membrane

• Flippase (phosphatidylserine and phosphatidylethanolamine – outer to inner mb)

• Floppase (phosphatidychlorine and cholesterol from – inner to outer mb)

• Scramblase (facilitating flip-flop of lipid)

• The interaction between ACP and cell membrane

• Hydrophobic interaction – between normal + ACP

• Electrostatic interaction – between normal + ACP

Alpha-helical form of anticancer peptide

• Penetrate plasma membrane 

• Penetrate nuclear membrane

• Penetrate mitochondrial membrane

Amino acid composition in anticancer peptide

• Predominantly contain G, K, L

• Cysteine residues in ACP – do not serve a role in selectivity and toxicity for cancer cells

• Internal proline in peptides – crucial for membrane interaction and conformational flexibility

• Glycine also increases the flexibility

• Tryptophan

• Entering the cell via endocytic pathway, and it proposes to bind major groove of nuclear DNA

• In brief, ACP should contain

• Cationic and hydrophobic residues – thus further forming secondary structure and affecting cancer cells

SAR of ACP

• Majority of ACP contains 21-30 aa

• Predominantly contain G, K, L

Classification of ACPs

This review – active peptides;

1. Molecularly targeted peptides – directly act on cancer cells

1. Peptide against only cancer cell but not healthy cell

1. Therapeutic peptide based on mode of mechanism

1. Pore-forming peptides – bind negatively charged molecules on cancer cell MB

2. Cell-penetrating peptides – translocate across plasma MB

3. Tumor-targeting peptides – bind to receptor on cell surface -- internalization

2. Peptides against both cancerous and normal cells

2. Guiding missile or biding peptides – using for transporting drugs

3. Cell-stimulating peptides

Membranolytic ACP

• Alpha-helical cationic amphipathic peptide 

Guiding missile peptides or binding peptides

• Delivery carrier

• Cationic, amphipathic, and hydrophobic peptide

Cell stimulate peptide