Abstract

A highly, interactive group of molecular biologists, pharmacologists, crystallographers, synthetic chemists and virologists propose to develop novel therapies for human HIV infections. Potential antiretroviral candidate compounds will include peptides, oligosaccharides and glycosylation inhibitors as well as fermentation products as a result of research in projects I through IV of this grant and through collaboration with Schering- Plough and Bristol Myers Corporation. Compounds synthesized will be screened by a comprehensive core to determine extent of antiretroviral activity, toxicity mechanism of action, pharmacology and/or toxicity. Unique small proteins will be crystallized to exploit the structure-function development of inhibitors of HIV replication.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI025784-03
Application #
3546794
Study Section
(SRC)
Project Start
1987-09-30
Project End
1992-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of Alabama Birmingham
Department
Type
Schools of Medicine
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294

  Publications

Comber, R N; Friedrich, J D; Dunshee, D A et al. (1994) Alpha-(1-->2)-, and alpha-(1-->3)-, and alpha-(1-->6)-linked thioglycosidic disaccharides: syntheses and anti-HIV testing of thiokojibiose octaacetate, thionigerose, and thioisomaltose. Carbohydr Res 262:245-55
Bray, M; Prasad, S; Dubay, J W et al. (1994) A small element from the Mason-Pfizer monkey virus genome makes human immunodeficiency virus type 1 expression and replication Rev-independent. Proc Natl Acad Sci U S A 91:1256-60
Srinivas, S K; Srinivas, R V; Anantharamaiah, G M et al. (1993) Cytosolic domain of the human immunodeficiency virus envelope glycoproteins binds to calmodulin and inhibits calmodulin-regulated proteins. J Biol Chem 268:22895-9
Salzwedel, K; Johnston, P B; Roberts, S J et al. (1993) Expression and characterization of glycophospholipid-anchored human immunodeficiency virus type 1 envelope glycoproteins. J Virol 67:5279-88
Hallenberger, S; Tucker, S P; Owens, R J et al. (1993) Secretion of a truncated form of the human immunodeficiency virus type 1 envelope glycoprotein. Virology 193:510-4
Johnston, P B; Dubay, J W; Hunter, E (1993) Truncations of the simian immunodeficiency virus transmembrane protein confer expanded virus host range by removing a block to virus entry into cells. J Virol 67:3077-86
Weidner, D A; Bridges, E G; Cretton, E M et al. (1992) Comparative effects of 3'-azido-3'-deoxythymidine and its metabolite 3'-amino-3'-deoxythymidine on hemoglobin synthesis in K-562 human leukemia cells. Mol Pharmacol 41:252-8
Srinivas, S K; Srinivas, R V; Anantharamaiah, G M et al. (1992) Membrane interactions of synthetic peptides corresponding to amphipathic helical segments of the human immunodeficiency virus type-1 envelope glycoprotein. J Biol Chem 267:7121-7
Comber, R N; Reynolds, R C; Friedrich, J D et al. (1992) 5,5-disubstituted hydantoins: syntheses and anti-HIV activity. J Med Chem 35:3567-72
Cretton, E M; Xie, M Y; Goudgaon, N M et al. (1992) Catabolic disposition of 3'-azido-2',3'-dideoxyuridine in hepatocytes with evidence of azido reduction being a general catabolic pathway of 3'-azido-2',3'-dideoxynucleosides. Biochem Pharmacol 44:973-80

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