Our long-term objective is to obtain a detailed understanding of the structure-function relationships of the tat (trans-activating protein) and art/rev (regulator of expression of virion proteins) proteins of human immunodeficiency virus (HIV), the trans- activating factors essential for the replication of the virus. For the research proposed here, our specific aims are: (1) Total chemical synthesis of the tat and art proteins and their structural analogues by the solid-phase methods. These proteins will be obtained in highly purified form and in sufficient quantity by applying both the stepwise strategy and the segment condensation strategy of peptide synthesis, the latter permitting preparation of analogues of the protein modified specifically at selected amino acid side-chain functions. Availability of chemically homogeneous tat and art proteins will permit studies leading to a better evaluation of their structure-trans-activating function relationship. (2) To determine selectively the role of these proteins on the HIV LTR-directed gene expression, both at the transcriptional and the translational levels. (3) To determine the functional domains by using rabbit antibodies against synthetic peptides representing selected regions of the proteins in competition experiments. (4) Use chemical modification approach to determine the role of side-chain functions of selected amino acid residues in binding to the nucleic acid sequences and to any other functional molecules. The results from these studies will provide an understanding of the elements involved in the tat and art regulated expression of the HIV structural proteins. Such an understanding could provide the basis for a rational chemotherapeutic approach directed against acquired immunodeficiency syndrome (AIDS).

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI027422-02
Application #
3141619
Study Section
Special Emphasis Panel (ARR (V1))
Project Start
1989-03-01
Project End
1992-02-28
Budget Start
1990-03-01
Budget End
1991-02-28
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Wistar Institute
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104