Functional Modulation of Peptide Structural Interaction Fingerprints upon Stereochemical Diversification.

Area of Science:

• Biochemistry and Molecular Biology
• Peptide Design
• Biophysics

Background:

• Polypeptide conformational space is limited with L-amino acids.
• Incorporating D-amino acids can create novel structures and functions.
• Electrostatic interactions are hypothesized to differ with stereochemical mutations.

Purpose of the Study:

• To investigate the expansion of polypeptide conformational space using L- and D-amino acids.
• To test the hypothesis that stereochemical mutations alter electrostatic interaction fingerprints and membrane penetration.
• To identify novel peptides for therapeutic applications, including anticancer and antibacterial uses.

Main Methods:

• Designed mutations in polypeptide chains to create novel architectures.
• Molecular dynamics simulations to examine peptide interaction with bacterial and mammalian cell membranes.
• In vitro studies using flow cytometry for cellular uptake and antibacterial assays against *Staphylococcus aureus* and *Escherichia coli*.

Main Results:

• In silico and in vitro results support the hypothesis that stereochemical mutations expand polypeptide conformational space and influence membrane interactions.
• Peptide YRC03 shows promise as an antibacterial agent against Gram-negative bacteria (*E. coli*).
• Peptide YRC01 demonstrates potential as a drug delivery vehicle for breast cancer treatment (MDA-MB-231 cells).

Conclusions:

• The study successfully expanded the polypeptide conformational space by incorporating D-amino acids.
• The findings support the potential of designed peptides as novel therapeutic agents.
• Two specific peptides, YRC03 and YRC01, are identified as promising candidates for further development.