Emory University

University of Georgia Research Foundation Inc

The UAB Research Foundation (The University of Alabama at Birmingham)

William M Shafer

James Travis

Jan Pohl

Neelesh Bangalore

Raymond F Schinazi

Chung K Chu

Jean-Pierre Sommadossi

Peptides which exhibit antimicrobial activity comparable to certain known antibiotics are provided. These peptides are related in sequence to amino acid sequences within Cathepsin G. A broad spectrum bactericidal peptide disclosed herein is RPGTLCTVAGWGRVSMRRGT (SEQ ID NO:22). It is active against Pseudomonas aeruginosa, Neisseria gonorrhoeae and Staphylococcus aureus. RRENTQQHITARRAIRHPQY (SEQ ID NO:19) and GKSSGVPPEVFTRFVSSFLPWIRTTMR (SEQ ID NO:26) also exhibited potent activity against P. aeruginosa strains, including clinical isolates. IIGGR (SEQ ID NO:1) and IVGGR (SEQ ID NO:2) act against both gram-negative and gram-positive bacterial strains. HPQYNQR (SEQ ID NO:3) and certain related peptides are also active against both gram-negative and gram-positive bacteria, including, but not limited to, strains of Escherichia coli, Neisseria gonorrhoeae, Staphylococcus aureus, Capnocytophage sputigena and Pseudomonas aeruginosa. The peptides of the present invention will be useful in pharmaceutical compositions useful in the treatment of prophylaxis of infections.

Antimicrobial peptides

Peptides which exhibit antimicrobial activity comparable to certain known antibiotics are provided. These peptides are related in sequence to amino acid sequences within Cathepsin G. A broad spectrum bactericidal peptide disclosed herein is RPGTLCTVAGWGRVSMRRGT (SEQ ID NO:22). It is active against Pseudomonas aeruginosa, Neisseria gonorrhoeae and Staphylococcus aureus. RRENTQQHITARRAIRHPQY (SEQ ID NO:19) and GKSSGVPPEVFTRFVSSFLPWIRTTMR (SEQ ID NO:20) also exhibited potent activity against P, aeruginosa strains, including clinical isolates. IIGGR (SEQ ID NO:1) and IVGGR (SEQ ID NO:2) act against both gram-negative and gram-positive bacterial strains. HPQYNQR (SEQ ID NO:3) and certain related peptides are also active against both gram-negative and gram-positive bacteria, including, but not limited to, strains of Escherichia coli, Neisseria gonorrhoeae, Staphylococcus aureus, Capnocytophage sputigena and Pseudomonas aeruginosa. The peptides of the present invention will be useful in pharmaceutical compositions useful in the treatment of prophylaxis of infections.

This invention provides compounds and pharmaceutical compositions that include compounds of the formula: ##STR1## in which A, B, and C are hydrogen, halogen, or azido; D is hydrogen, halogen, azido, or OH; A and B or C and D can be replaced with a double bond; R is an aldohexose, aldohexosamine, or N-acetyl aldohexosamine, W is O or S; X is O, S, or CH.sub.2 ; Y is a purine or pyrimidine base, Z is C, S, or O, and wherein when Z is S or O, A and C are not present. The compounds of this inverntion have enhanced pharmaceutical or biological activity or increased intracellular absorption compared to the corresponding parent nucleoside as a function of the 5'-diphosphohexose moiety. Many of these compounds have antiviral, including anti-HIV, activity. Others have antibacterial activity. In one embodiment, the invention is a method to treat HIV infection and opportunistic infections concomitantly.

5'-diphosphohexose nucleoside pharmaceutical compositions

Growing community of inventors

Stone Mountain, GA, United States of America

William M Shafer