University of Pittsburgh

Timothy A Mietzner

Ronald C Montelaro

Sarah Burroughs Tencza

Philip C Hanna

Bruce A McClane

Described herein are peptides having antimicrobial activity (antimicrobial peptides). The antimicrobial peptides, designated LBU, WLBU and WR, are analogs of the Lentivirus Lytic Peptide 1 (LLP1) amino acid sequence. The antimicrobial peptides are monomers or multimers of peptides referred to as the Lytic Base Unit (LBU) peptides, derived from the LLP1 analogs and also having antimicrobial activity. Also described herein are using the peptides in a variety of contexts, including the treatment or prevention of infectious diseases. Methods of killing fungi, such asandspecies, and bacteria, such as, are provided herein. Methods of neutralizing enveloped viruses, such as poxvirus, herpesvirus, rhabdovirus, hepadnavirus, baculovirus, orthomyxovirus, paramyxovirus, retrovirus, togavirus, bunyavirus and flavivirus, including influenza virus and HIV-1 also are provided herein. Solid phase substrates and peptide-cargo complexes comprising the peptides also are provided.

Virus derived antimicrobial peptides

The invention is directed to peptides having antimicrobial activity (antimicrobial peptides). The antimicrobial peptides of the present invention are analogs of the Lentivirus Lytic Peptide 1 (LLP1) amino acid sequence. The invention is further directed to peptides referred to as the Lytic Base Unit (LBU) peptides derived from the LLP1 analogs, also having antimicrobial activity. In addition, the present invention is also directed to methods of using the peptides in a variety of contexts, including the treatment or prevention of infectious diseases. The antimicrobial LLP1 analog peptides and the LBU peptides (collectively eLLPs) may be highly active under high salt conditions and in biologic fluids. In addition, the eLLPs are effective when presented either in soluble form, or when attached to a solid surface. Furthermore, the peptides of the present invention are selectively active against a wide variety of bacterial pathogens and exhibit minimal toxicity to eukaryotic cells in vitro and in vivo.

The invention is directed to antimicrobial peptides which correspond in sequence to selective amino acid sequences in viral transmembrane proteins. In particular, the proteins are derived from lentiviruses, primarily HIV and SIV. The peptides comprise arginine-rich sequences, which, when modeled for secondary structure, display a high amphipathicity and hydrophobic moment. They are highly inhibitory to microorganisms, while being significantly less active in regard to mammalian cells. As a result, the peptides of the invention may be defined as selective antimicrobial agents. The invention is also directed to antimicrobial peptides which are structural and functional analogs and homologs of the peptides and which exhibit selective inhibitory activity towards microorganisms. The invention is also directed to pharmaceutical compositions comprising the antimicrobial peptides of the invention and to methods for their use in inhibiting microbial growth and treatment of microbial infections.

Antimicrobial peptides

Escherichia coli strains that produce recombinant Clostridium perfringens type A enterotoxin toxoids from a Clostridium perfringens type A enterotoxin gene fragment encoding the Clostridium perfringens type A enterotoxin binding domain subcloned into an expression vector for forming plasmids are disclosed. The Clostridium perfringens type A enterotoxin toxoids of this invention recognize, irreversibly bind to and saturate receptor sites on intestinal membranes and, thus effectively compete for these receptor sites with Clostridium perfringens type A enterotoxin. The toxoids of this invention may be used to treat the symptoms of Clostridium perfringens food poisoning in patients. Vaccines are also disclosed that may be used to prevent the symptoms of Clostridium perfringens food poisoning in patients. Processes for preparing the plasmids and toxoids of this invention and for using the toxoids and vaccines of this invention are also provided.

Growing community of inventors

Pittsburgh, PA, United States of America

Timothy A Mietzner