Synthesis and SAR studies of antimicrobial peptide Leucocin A

• Author / Creator

  Bodapati, Krishna Chaitanya

• In this study, we report the synthesis of a potent antimicrobial peptide Leucocin A (LeuA) using two solid phase peptide synthesis methods. One of the methods, native chemical ligation, gave high yield (12.5%) of 37-residue LeuA and can be utilized in the synthesis of LeuA to perform structure-activity relationship (SAR) studies. Three analogues (1-3) of LeuA were designed and synthesized to explore the SAR in the N-terminal domain of LeuA. In the analogues, N-terminal -sheet residues Cys9-Ser15 of the native peptide were replaced with shorter -turn motifs. Such replacement abolished the antimicrobial activity in all the analogues. Circular dichroism spectroscopy suggested that only analogue 1 adopted similar folding as LeuA. Therefore, 1 was able to competitively inhibit the activity of native LeuA. However, analysis of the secondary structure of 1 using molecular dynamics simulations suggested lack of -sheet formation in the N-terminal region compared to LeuA emphasizing the role of proper folding and sequence in the activity of class IIa bacteriocins.

• Subjects / Keywords

  • Antimicrobial peptide, leucocin a, bacteriocin

• Graduation date

  Fall 2011

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3J707

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.