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Design and synthesis of peptidomimetics as antibacterials, antivirals and HIV-1 synthetic vaccine candidates

English title Design and synthesis of peptidomimetics as antibacterials, antivirals and HIV-1 synthetic vaccine candidates
Applicant Robinson John A.
Number 116176
Funding scheme Project funding
Research institution Organisch-chemisches Institut Universität Zürich
Institution of higher education University of Zurich - ZH
Main discipline Organic Chemistry
Start/End 01.08.2007 - 31.07.2010
Approved amount 286'169.00
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Keywords (11)

Peptide; Protein; biomimetic; inhibitor; Vaccine; Antibiotic; peptidomimetic; antiviral; HIV; protein epitope mimetics; drug discovery

Lay Summary (English)

Lead
Lay summary
The research is concerned with the design and study of small synthetic molecules that mimic surface epitopes on folded peptides and proteins (protein epitope mimetics). Surface epitopes typically mediate protein-protein interactions, and so epitope mimetics are of great interest in the design and development of new biologically active molecules, in particular, new drug and vaccine candidates. In this project new peptidomimetics will be investigated, including: 1) a new class of antibiotics discovered recently in our lab acting against the important Gram negative human pathogen Pseudomonas aeruginosa. The main focus of the work is on elucidating the mode of action of these antibiotics, which is currently unknown. P. aeruginosa is a serious human pathogen, and clinical isolates frequently show resistance to the exisiting clinically used antibiotics. The new molecules studied here may therefore become a valuable new weapon in the fight against life-threatening infections with these bacteria; 2) a new class of molecule that bind specifically to RNA, and in doing so inhibit the life cycle of the human immunodeficiency virus-1 (HIV-1). Molecules that bind RNA are increasingly being recognized as a potentially valuable source of new drug leads. In an extension of earlier work, we plan to prepare a new class of RNA ligands that bind and inactivate an RNA molecule essential to HIV. The aim is to increase the potency and specificity of these molecules, and study how they interact with RNA. These molecules are potentially of interest as novel antiviral agents; and 3) new peptide mimetics based on epitopes on surface proteins on HIV-1, will be developed that can be used to elicit antibodies that neutralize HIV-1. Thus the aim here is to identify new leads for development as potential vaccine candidates against HIV. The peptidomimetics are designed to mimic key epitopes on HIV structural proteins, and these are delivered to the immune system on the surface of virus-like particles. In this way, powerful humoral immune responses should be elicited, that neutralize the virus.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

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Associated projects

Number Title Start Funding scheme
103984 1. Protein Epitope Mimetics and Biomedical research and 2. The Biosynthesis of the Glycopeptide Antibiotic Vancomycin 01.06.2004 Project funding
129724 Design and applications of protein epitope mimetics 01.06.2010 Project funding
129724 Design and applications of protein epitope mimetics 01.06.2010 Project funding
146381 Synthetic Protein Epitope Mimetics and Applications as Anti-infectives 01.06.2013 Project funding

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