Due to their clinical potential, antimicrobial peptides (AMPs) have piqued the interest of researchers, health professionals, and pharmaceutical companies in recent years. These peptides have a low molecular weight and exhibit a broad spectrum of antimicrobial and immunomodulatory activity against gram-positive and negative bacteria, viruses, and fungi. Additionally, these peptides exhibit enhanced efficacy, increased specificity, decreased drug interaction, low-level toxicity, direct attacking capabilities, and biological diversity. As a result, pharmaceutical companies are conducting clinical trials to determine the potential therapeutic value of these peptides [1]. By interacting with negatively charged phospholipids, cationic AMPs can destabilize microbial cell membranes. Additionally, several peptides can cause cytotoxicity in human cancer cells by binding to negatively charged phosphatidylserine moieties on the outer surface of cancer cell plasma membranes [2]. AMPs are a new source of anticancer drugs that are low in toxicity and have the potential to overcome tumor resistance to conventional chemotherapy [3].
Although the mechanism of action of host defense peptides is unknown, electrostatic attraction between negatively charged cancer cell components and positively charged AMPs is required for efficient binding and degradation of cancer cell membranes [4]. Natural AMPs are found in a wide range of organisms, are unstable with a short half-life, and have the potential to cause hemolysis. It is vital and essential to produce synthetic and long-lasting AMP analogues that overcome the inherent limitations of their natural peptides and also address potential issues for therapeutic candidates [5]. Reduced cholesterol levels in cancer cells may result in increased membrane fluidity, which aids AMP-induced apoptosis [6]. AMPs have obtained a lot of interest as anticancer drugs as they can selectively target cancer cells instead of healthy cells [7, 8].
Antimicrobial peptides containing tryptophan have been shown to improve cytotoxicity against non-small cell lung adenocarcinoma A549 cells [9]. Proline-rich AMPs (p1922) have been investigated in a primary gingival fibroblast cell line and a squamous cancer cell line [10]. PR-39 is an antimicrobial peptide with a high proline-arginine content derived from neutrophils. It is a curly antimicrobial peptide with an irregular shape. It has a moderate inhibitory effect on tumour cells but a strong inhibitory effect on normal human embryonic kidney 293T cells [11]. The tryptophan residue on cell-penetrating peptides is critical for their entry into cancer cells, which involves an endocytic pathway and binding to the nuclear DNA's primary groove [12]. The epidermal growth factor receptor (EGFR), a member of the ErbB receptor tyrosine kinase (TK) family, plays an important role in the development and progression of non-small-cell lung cancer (NSCLC). Tyrosine kinase inhibitors (TKIs) targeting the human EGFR has now have a standard treatment regimen in the clinic for patients with advanced EGFR mutant NSCLC. Since EGFR-mutated tumors rely on EGFR activity to stimulate downstream signalling pathways, there is a chance that such cancers can be treated with peptide-based TKIs that block EGFR signalling [13]. We addressed significant advancements in the importance of tryptophan, proline, and arginine-rich AMPs as anticancer agents, as well as their binding affinity for the EGFR kinase and estimation of stable kinetics using molecular dynamics simulations. In addition, we did bilayer dynamics between the screened peptide and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylserine (POPS) to figure out stable conformations.