The proposed research is aiming at i) developing new and effective methods for the asymmetric synthesis of beta-lactams and azetidines based on addition-cyclizations and cycloadditions: By means of the effective methods developed, a variety of chiral synthetic building blocks for peptide analogs, poly-beta-lactams, and polyazetidines will be synthesized: These new methods are also beneficial to the synthesis of beta-lactam antibiotics in general, ii) synthesizing """"""""deoxo"""""""" analogs of brain peptides and labelled peptides for neurobiological studies using the """"""""azetidine synthon method"""""""" and """"""""beta-lactam synthon method"""""""": The behavior of new """"""""deoxo"""""""" analogs of enkephalin and vasopressin toward enzymatic degradation in the brain will be studied: A new method for the stereo- and regiospecific labelling of peptides will be developed and established using a stereospecific cleavage of beta-lactam with tritium or deuterium, iii) synthesizing chiral cyclic poly-beta-lactams and polyazetidines as potential ionophores or reagents for endonucleolytic cleavage of DNA; metal ion binding ability of these chiral heterocyclic ligands will be investigated and several metal complexes will be synthesized, which are expected to intercalate into double-strand DNA and cleave it, and iv) biological study and biological activity screening in collaboration with a neurobiologist, a biochemist and the institutions which have excellent testing facilities.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM033665-02
Application #
3283565
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1986-09-01
Project End
1989-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
State University New York Stony Brook
Department
Type
Schools of Arts and Sciences
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794