The long term goals of this research involve modification of the peptidyltransferase (PTC) center in bacterial ribosomes to enable the incorporation of very unusual amino acids not recognized by wild- type ribosomes. In recent years, we have described the selection of modified ribosomes and their use in incorporating D-amino acids, beta amino acids, dipeptides and dipeptidomimetric cassettes into proteins. During the five years of proposed research, the focus of efforts will be on the introduction of conformationally constrained cyclic dipeptides and nucleobase amino acids into specific proteins (both as mono- and dipeptides), creating species that have novel properties enabling enhanced analysis of protein function to be realized, as well as the analysis of specific conformational properties essential for enzyme function and strategies for enhancing (and potentially modifying) protein-DNA recognition.

Public Health Relevance

The present project is aimed at employing modified bacterial ribosomes to incorporate dipeptides and dipeptide analogues into specific proteins. These modified proteins will have unique properties, enabling enhanced analysis of protein behavior to be realized, including an understanding of specific conformational properties essential for enzyme function and strategies for enhancing (and potentially modifying) protein-DNA recognition.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM121367-03
Application #
9693736
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Bond, Michelle Rueffer
Project Start
2017-07-15
Project End
2021-05-31
Budget Start
2019-06-01
Budget End
2020-05-31
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Arizona State University-Tempe Campus
Department
Miscellaneous
Type
Organized Research Units
DUNS #
943360412
City
Tempe
State
AZ
Country
United States
Zip Code
85287