The specific aims of the proposed research are the syntheses of (1) bicyclic peptides with varying cavity sizes to serve as model cation-binding moities, (2) cyclic peptides with oxazoline or thiazole groups, (3) linear peptides having amino acid sequences of a transmembrane portion of bacteriorhodopsin, and (4) """"""""leader"""""""" sequences of one or more membrane proteins. The bicyclic peptides should approximate more closely than previous models the ion-binding sites of metalloenzymes. Investigations are planned of both the specificity and quantitative aspects of ion binding. The cyclic peptides incorporating heterocyclic ring systems relate to recently discovered naturally-occurring cyclic peptides. In all four categories listed above, the peptides synthesized will be used for conformational investigations, both in solution and ultimately in lipid bilayer systems such as vesicles. In some cases it will be necessary to synthesize the peptides with NMR labels such as 19F, 13C, and 2H, which will allow conformational determinations of both greater precision and with the capability of solving peptide structures of greater complexity. The compounds prepared under this grant will be used for conformational investigations under another on-going NIH research grant. The main physical techniques to be used for solution conformational investigations will be NMR spectroscopy and circular dichroism. The long-term objectives of this research are to increase our understanding of the mode of action of proteins and the relationships between the structure of proteins and their biological functions. The importance to health of understanding both the specificity of cation-binding to peptides and proteins and the modes of ion transport in cells and tissues is well-documented in biochemical and medical literature.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK010794-20
Application #
3224718
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1977-01-01
Project End
1986-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
20
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115