Effect of substituting glutamine with lysine on structural and biological properties of antimicrobial peptide
Hai Bui Thi Phuong1, Van Anh Tran1, Khoa Nguyen Ngoc1
1Faculty of Pharmacy, Phenikaa University, Hanoi, 12116, Vietnam.
Abstract:
The natural antimicrobial peptide Polybia-MP1 is a promising candidate for developing new treatment therapy for infection and cancer. It showed broad-spectrum antimicrobial and anticancer activity with high safety on healthy cells. However, previous sequence modification usually resulted in at least one of two consequences: a notable increase in hemolytic activity or a considerable decrease in activity against Gram-negative bacteria and cancer cells. Herein, a new approach was applied by replacing the amino acid Glutamine at position 12 with Lysine and generating the MP1-Q12K analog. Our preliminary data suggested an enhancement in antibacterial and antifungal activity, whereas the anticancer and hemolytic activity of the two peptides were comparable. Moreover, MP1-Q12K was found to be less self-assembly than Polybia-MP1, which further supports the enhancement of antimicrobial properties. Hence, this study provides new information regarding the structure-activity relationships of Polybia-MP1 and support for the development of potent, selective antimicrobial peptides.
Insights
A modified antimicrobial peptide, MP1-Q12K, shows enhanced antibacterial and antifungal activity. This peptide offers a promising new avenue for developing potent and selective antimicrobial therapies with improved safety profiles.
Area of Science:
- Biochemistry
- Molecular Biology
- Drug Discovery
Background:
- The natural antimicrobial peptide Polybia-MP1 exhibits broad-spectrum antimicrobial and anticancer properties with high safety.
- Previous modifications of Polybia-MP1 often led to increased hemolytic activity or reduced efficacy against Gram-negative bacteria and cancer cells.
Purpose of the Study:
- To investigate the structure-activity relationships of Polybia-MP1 by creating a novel analog, MP1-Q12K.
- To evaluate the antimicrobial, anticancer, and hemolytic activities of MP1-Q12K compared to the native peptide.
Main Methods:
- Site-directed mutagenesis was employed to replace Glutamine at position 12 with Lysine, generating the MP1-Q12K analog.
- Comparative analysis of antimicrobial (antibacterial, antifungal), anticancer, and hemolytic activities between Polybia-MP1 and MP1-Q12K.
Main Results:
- MP1-Q12K demonstrated enhanced antibacterial and antifungal activity compared to Polybia-MP1.
- Anticancer and hemolytic activities of MP1-Q12K were comparable to the native peptide.
- MP1-Q12K exhibited reduced self-assembly compared to Polybia-MP1, correlating with enhanced antimicrobial properties.
Conclusions:
- The substitution of Glutamine with Lysine at position 12 in Polybia-MP1 yields an analog with improved antimicrobial efficacy.
- MP1-Q12K represents a promising candidate for developing potent and selective antimicrobial peptides with potential applications in infection and cancer treatment.
