Synthesis and SAR studies of antimicrobial peptide Leucocin AReport as inadecuate




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antimicrobial peptide, leucocin a, bacteriocin

Bodapati, Krishna Chaitanya

Supervisor and department: Dr.Kamaljit Kaur pharmacy

Examining committee member and department:

Department: Faculty of Pharmacy and Pharmaceutical Sciences

Specialization:

Date accepted: 2011-09-01T21:45:20Z

Graduation date: 2011-11

Degree: Master of Science

Degree level: Master's

Abstract: 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.

Language: English

DOI: doi:10.7939-R3J707

Rights: License granted by Krishna Bodapati krishnac@ualberta.ca on 2011-09-01T06:14:36Z GMT: Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of the above terms. The author reserves all other publication and other rights in association with the copyright in the thesis, and except as herein provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.





Author: Bodapati, Krishna Chaitanya

Source: https://era.library.ualberta.ca/


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University of Alberta Synthesis and SAR studies of Antimicrobial Peptide Leucocin A By Krishna Chaitanya Bodapati A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Master of Science In Pharmaceutical Sciences Faculty of Pharmacy and Pharmaceutical Sciences ©Krishna Chaitanya Bodapati Edmonton, Alberta Fall 2011 Edmonton, Alberta Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only.
Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the authors prior written permission. Dedication I would like to dedicate this thesis to my parents Venkateswarlu and Rama Devi who have never failed to give me moral and financial support and to my brother Baswanth Maharshi for his love, and encouragement. Abstract 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 Nterminal 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 ...





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