Nucleic acids encoding antimicrobial peptides

Details Nucleic acids encoding antimicrobial peptides Nucleic acids encoding antimicrobial peptides

1999-06-15

2001-07-17

Carlson, Karen Cochrane (Department: 1653)

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

C536S023100, C536S023500, C530S350000, C530S300000, C530S324000, C530S329000, C514S012200, C435S006120, C435S007100, C435S320100, C435S068100, C435S069100

Reexamination Certificate

active

06262243

ABSTRACT:

BACKGROUND OF THE INVENTION
This invention relates generally to antimicrobial compounds and agents. More specifically, it concerns novel broad spectrum antimicrobial peptides containing a tryptophan triplet and their derivatives which exhibit antimicrobial activity with low immunogenicity. Also provided are methods of microbicidal or microbistatic inhibition of microbial growth using pharmaceutical and non-pharmaceutical compositions wherein such antimicrobial peptides are an active component.
Infectious diseases have plagued human populations throughout history and continue to cause millions of deaths each year. Although widespread use of vaccines and drug therapy has dramatically reduced mortality due to infectious disease in developed countries, infectious diseases continue to be the leading cause of death in third world countries. It is estimated that over 600 million people are infected with tropical diseases, resulting in some 20 million deaths each year. Even in developed countries, infectious disease organisms spread misery to untold millions each year.
Individuals with an immunodeficiency disease are particularly at risk for infectious disease. The basic clinical manifestations are frequent, prolonged, severe infections, which are often caused by organisms of normally low pathogenicity. The hallmarks of immunodeficiency disease are recurrent bacterial or fungal infections. The clinical manifestations range from mild skin infections to life-threatening systematic infections. Common infectious organisms include
Staphylococcus aureas, Streptococcus pneumoniae, Escherichia coli
, and various species of Pseudomonas, Candida, and Aspergillus. Because of the seriousness of many infectious diseases, scientists continue to search for effective means of killing or controlling such organisms which, at the same time, exhibit low immunogenicity.
It has been speculated that cathelin, a protein isolated from pig blood leukocytes, is the N-terminal fragment of a pig homolog of a novel family of antibacterial peptides. The cDNA sequence of a putative homolog of this proline/arginine-rich antibacterial porcine protein was described by Joze Pungercar, et al., “Molecular cloning of a putative homolog of proline/arginine-rich antibacterial peptides from porcine bone marrow,”
FEBS,
336:284-88 (1993). However, the potentially antimicrobial portion of this proposed 228-amino acid peptide is 101 amino acids long which is too long and too large for production and effective utilization as an antimicrobial agent.
SUMMARY OF THE INVENTION
Among the several objects of the invention, therefore, may be noted the provision of broad spectrum antimicrobial peptides having low immunogenicity which can be readily synthesized; the provision of antimicrobial pharmaceutical and non-pharmaceutical compositions containing these peptides and methods of inhibiting microbial growth and treating infectious diseases using these compositions.
Briefly, therefore, the present invention is directed to broad spectrum antimicrobial peptides containing a tryptophan triplet of at least 10 amino acid residues in length. Preferably, the antimicrobial peptides of the invention have substantially the same sequence as defined by SEQ ID NO: 1. The present invention is further directed to compositions which have an antimicrobial peptide of the invention as their active component. In yet another aspect of the invention, a method of microbicidal or microbistatic inhibition of microbial growth in a microbial growth sustaining environment is provided.
Other objects and features will be in part apparent and in part pointed out hereinafter.


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