Graduation Year
2014
Document Type
Thesis
Degree
M.D.
Degree Granting Department
Chemistry
Major Professor
Jianfeng Cai, Ph.D.
Committee Member
David Merkler, Ph.D.
Committee Member
Mark McLaughlin, Ph.D.
Committee Member
Umesh Jinwal, Ph.D.
Keywords
Antimicrobial peptides, host defense peptides, amphipathicity, biofilms
Abstract
The emergent resistance of bacteria against the conventional antibiotics has motivated the search for novel antimicrobial agents. Nature abounds with a number of antimicrobial peptides that are a part of our innate immune system and protect us against a variety of pathogenic bacteria. While they are broad-spectrum in their activity and show less drug-resistance induction, their intrinsic metabolic stability limits their potential therapeutic applications. Herein we describe the development of novel broad-spectrum bioactive antimicrobial peptidomimetics AA-peptides. AApeptides were designed based on chiral PNA backbone. Substitution of nucleobases yields AApeptides that are resistant to proteolysis and capable of mimicking peptides. Two types of AApeptides are discussed in this dissertation "[aacute]-AApeptides" and " ã-AApeptides" The therapeutic potential of these AApeptides were accessed by conducting antibacterial assays against a series of both gram-positive, gram-negative bacteria and fungi. These oligomers were characterized using MALDI-TOF and Circular Dichroism spectroscopy (CD). Their invitro toxicity was evaluated against human erythrocytes .We attempted to study their mechanism of action via membrane depolarization assay. We have successfully identified them as antimicrobial agents, pro-inflammatory immune response suppressing agents and as anti-biofilm agents.
Scholar Commons Citation
Padhee, Shruti, "Insights into [aacute]-AA peptides and ã-AA peptides as broad spectrum antimicrobial peptidomimetics and as anti-biofilm agents" (2014). USF Tampa Graduate Theses and Dissertations.
https://digitalcommons.usf.edu/etd/5091
