###### Abstract
In another study, computational docking and screening methods were used to identify the targeting ability of the green tea derived polyphenol epigallocatechin gallate (EGCG) toward RSK2 as a novel molecular target [22; 23]. Both molecular docking and molecular dynamics (MD) studies are useful in determining the efficacy and stability of receptor targeting with various ligands [24]. For example, in a recent study, it was shown that polyphenols such as papyriflavonol A and kazinol F interacted with the main protease (MPro) enzyme of SARS-CoV-2 and may be developed as potential drugs [25]. In another study, [PERSON] and coworkers tested several polyphenols using docking and MD and showed that the methoxy flavonoid acacetin formed a stable complex with the active site of aldose reductase receptor; thus, it may potentially be developed as an inhibitor of the enzyme [26]. In this work, we have designed anticancer peptides that were conjugated with chlorogenic acid (CGA), carnostic acid (CSA), gallic acid (GLA), and rosmarinic acid (RMA) to develop new polyphenol-peptide conjugates for targeting receptors over-expressed in breast cancer cells. We chose to study three receptors. Estrogen receptor alpha (ER\(\alpha\)), which is over-expressed in hormone sensitive breast cancer; peroxisome proliferator-activated receptor alpha (PPAR-\(\alpha\)), which is over-expressed in triple negative breast (TNBC) and ER positive cancer cells [27]; and epidermal growth factor receptor (EGFR), which is also over-expressed in TNBC [28]. The anticancer peptides were designed by performing point mutations on the known antitumor peptide sequence Y-H-W-Y-G-Y-T-P-Q-N (Pep). This peptide sequence is a truncated form of Y-H-W-Y-G-Y-T-P-Q-N-V-I; both sequences have previously been shown to bind to epidermal growth factor receptor (EGFR) [29]. Additionally, in recent studies, it has been shown that there is involvement of crosstalk between estrogen receptors (ERs) and EGFR in breast cancer cells and that expression of extracellular secreted and cell bound proteoglycans are involved in cancer progression [30]. We therefore sought to probe the possible targeting abilities of this sequence not only for EGFR, but also for ER-\(\alpha\), as well as alternative receptors overexpressed in breast cancer cells (PPAR-\(\alpha\)). To enhance receptor targeting, we designed four peptide sequences by point mutation of the original peptide Y-H-W-Y-G-Y-T-P-Q-N at positions 1, 2, 8, and 10. For Mutation 1, **Y**, which was in the first position, was substituted with **F**, thus designing the sequence **F**-H-W-Y-G-Y-T-P-Q-N (Mut1). For Mutation 2, **H**, which was in the second position, was substituted with **I**, producing the sequence Y-I-W-Y-G-Y-T-P-Q-N (Mut2) and significantly altering the properties. For Mutation 3, **P** at position 8 was changed to **H**, making Y-H-W-Y-G-Y-T-H-Q-N (Mut3). For Mutation 4, **N** at position 10 was substituted with **D**, making Y-H-W-Y-G-Y-T-P-Q-D (Mut4). Thus, Mut1 replaces Y with F, which are both hydrophobic. In previous studies, as indicated by [PERSON] and co-workers [29] replacing Y to F increased cell-adhesion toward both MCF-7 and MDA-MB-231 cells. Mutation 2 was intended to explore the effect of increased hydrophobicity by changing H to I. Mutation 3, which substituted Pro with His, was intended to increase the polarity of the peptide and reduce the effects of rigidity induced by Pro. Finally, N was substituted by D to examine the effect of a negatively charged residue at the C-terminal. Each of these peptides were then conjugated to CGA, CSA, GLA or RMA. The sequences of the peptides and chemical structures of the conjugates are shown in Tables 1 and 2.