Objective
This proposal aims to develop a method that utilizes aminoglycoside acetyltransferases for the in-vitro generation of novel and clinically potent N-acylated aminoglicosides. I propose an efficient and unconventional chemoenzymatic approach for the production of a large variety of N-acylated aminoglycosides. By accomplishing the goals of the proposed research, I will introduce a new and important tool that will provide access to previously unknown and synthetically challenging aminoglycosides. This study may lead to the discovery of new aminoglycosides with superior activity against resistant strains as well explore directions to reduce their toxic side effects. The proposed strategy offers an elegant solution to the following problem: There are no existing general synthetic methodologies for the regio-selective N-acylation of aminoglycosides. Indeed, there are no efficient solutions as to how to chemically modify a specific amine group on an aminoglycoside that contain a series of chemically identical amines. The few existing examples require substantial efforts in both syntheses as well as in cost, and are limited to very specific cases. The three specific aims of the proposed research are: 1) To chemically synthesize coenzyme A (CoA) derivatives as substrates for the chosen AACs. Some CoAs will be utilized to directly produce the desired analogs. Other CoAs will serve as handles for the generation of libraries of new compounds after further derivatization by nucleophilic displacement or click chemistry. 2) We plan to perform biochemical studies on AACs that will target three different positions to be N-acylated on a large number of aminoglycosides. We will study enzyme promiscuity and generate libraries of new compounds using our methodology. 3) We plan to scale-up and test for antibacterial activity some of our novel analogs in search of improved antibacterial activity.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
- natural sciences chemical sciences organic chemistry amines
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2009-RG
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
69978 Tel Aviv
Israel
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.