THE SIR SUPPLIED DR. JAMES WITH 1G OF D, L-ARGININE-GUANIDO 13C, 15N2. ARGININE WITH 13C AND 15N LABELED IN THE GUANIDO GROUP IS OBTAINED FROM THE NATIONAL STABLE ISOTOPE RESOURCE AT LOS ALAMOS NATIONAL LABORATORY. THIS LABELED ARGININE IS INCORPORATED INTO A 25 AMINO ACYL PEPTIDE WHICH CONTAINS THE RNA BINDING DOMAIN OF THE TAT PROTEIN FROM HIV-1 AND HAS BEEN SHOWN TO PROMOTE HIV-1 REPLICATION CELLS. WHILE THE 25-MER HAS HAD ITS SOLUTION STRUCTURE DETERMINED VIA HOMONUCLEAR PROTON NMR STUDIES, THE SIDE-CHAIN PROTON RESONANCES OF THE SEVERAL ARGININES CANNOT BE RESOLVED IN THE SPECTRA. PLACING THE LABELED ARGININE AT THE POSITION CORRESPONDING TO R52 IN HIV-1 TAT IS IMPORTANT IS SUBSEQUENT STUDIES OF THE BIOLOGICALLY ACTIVE TAT PEPTIDE WITH TAR, THE RNA TO WHICH IT BINDS IN VIRAL REPLICATION. R52 HAS BEEN DEMONSTRATED TO BE ESSENTIAL FOR TAT ACTIVITY. THE STRUCTURE OF THIS SELECTIVELY LABELED PEPTIDE BOUND TO TAR SHOULD BE MUCH BETTER DEFINED BY USE OF THE LABELED ARG. CONSEQUENTLY, THE STRUCTURE DETERMINED SHOULD PROVIDE A BETTER TARGET FOR DEVELOPMENT OF A DRUG TO COMBAT AIDS.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
3P41RR002231-12S1
Application #
3723126
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
1996
Total Cost
Indirect Cost
Name
Los Alamos National Lab
Department
Type
DUNS #
City
Los Alamos
State
NM
Country
United States
Zip Code
87545
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