Abstract

The proposed research is a biophysical study of biological lipid membranes and membrane-active peptides. It relies primarily on methods of infrared (IR) spectroscopy and lipid film balance techniques.
The research aims to : (1) determine the conformation and orientation of membrane-bound cecropin A, (2) characterize the process of membrane recognition by cecropin A and sarcotoxin 1A, (3) verify an oligomeric model for membrane recognition by the influenza fusion peptide, and (4) develop essential software and instrumentation. This research will improve the understanding of the fundamental biophysical processes underlying peptide-lipid interactions in which peptides undergo programmed conformational changes upon encountering a lipid membrane. These processes are critical to understanding viral fusion--an important pathogenic mechanism in human infections such as influenza, measles, and HIV--and to understanding the role of naturally occurring antimicrobial peptides in host defense against infection.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM054617-03
Application #
2910260
Study Section
Biophysical Chemistry Study Section (BBCB)
Project Start
1997-05-01
Project End
2001-04-30
Budget Start
1999-05-01
Budget End
2000-04-30
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Pharmacology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Haque, Md Emdadul; Koppaka, Vishwanath; Axelsen, Paul H et al. (2005) Properties and structures of the influenza and HIV fusion peptides on lipid membranes: implications for a role in fusion. Biophys J 89:3183-94
Koppaka, Vishwanath; Paul, Cynthia; Murray, Ian V J et al. (2003) Early synergy between Abeta42 and oxidatively damaged membranes in promoting amyloid fibril formation by Abeta40. J Biol Chem 278:36277-84
Hong, Robert W; Shchepetov, Mikhail; Weiser, Jeffrey N et al. (2003) Transcriptional profile of the Escherichia coli response to the antimicrobial insect peptide cecropin A. Antimicrob Agents Chemother 47:1-6
Murray, Ian V J; Giasson, Benoit I; Quinn, Shawn M et al. (2003) Role of alpha-synuclein carboxy-terminus on fibril formation in vitro. Biochemistry 42:8530-40
Jusuf, Sutjano; Loll, Patrick J; Axelsen, Paul H (2003) Configurational entropy and cooperativity between ligand binding and dimerization in glycopeptide antibiotics. J Am Chem Soc 125:3988-94
Jusuf, Sutjano; Loll, Patrick J; Axelsen, Paul H (2002) The role of configurational entropy in biochemical cooperativity. J Am Chem Soc 124:3490-1
Koppaka, V; Axelsen, P H (2000) Accelerated accumulation of amyloid beta proteins on oxidatively damaged lipid membranes. Biochemistry 39:10011-6
Silvestro, L; Weiser, J N; Axelsen, P H (2000) Antibacterial and antimembrane activities of cecropin A in Escherichia coli. Antimicrob Agents Chemother 44:602-7
Silvestro, L; Axelsen, P H (2000) Membrane-induced folding of cecropin A. Biophys J 79:1465-77
Silvestro, L; Axelsen, P H (1999) Fourier transform infrared linked analysis of conformational changes in annexin V upon membrane binding. Biochemistry 38:113-21

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