Peptide Inhibitors of Phosphoglycerate Mutase and Methods of Use

Content Provider	The Lens
Abstract	Disclosed herein are isolated peptides inhibit activity of a cofactor-independent phosphoglycerate mutase. In some examples, the isolated peptide is 6-20 amino acids long and includes the amino acid sequence of any one of SEQ ID NOs: 1-22 or 54, an analog or derivative thereof, or a pharmaceutically acceptable salt or ester thereof. In some examples, the peptide is a cyclic peptide with an N-terminal ring of 6-15 amino acids (for example, 6-10 amino acids) and a C-terminal linear portion of 1-9 amino acids (for example, 3-8 amino acids. Also disclosed h are methods of treating or inhibiting an infection in a subject, including administering to the subject an effective amount of a composition including one of more of the disclosed peptides, or analogs or derivative thereof, or pharmaceutically acceptable salts or esters thereof.
Related Links	https://www.lens.org/lens/patent/011-793-354-350-06X/frontpage
Language	English
Publisher Date	2019-06-06
Access Restriction	Open
Content Type	Text
Resource Type	Patent
Jurisdiction	United States of America
Date Applied	2017-08-10
Applicant	Univ Tokyo New England Biolabs Inc Us Health
Application No.	201716324424
Claim	An isolated cyclic peptide comprising the amino acid sequence of any one of SEQ ID NOs: 1-6, 10-20, or 54-69 wherein the peptide includes an N-terminal ring structure of 7-13 amino acids and a C-terminal linear portion of 1-7 amino acids, an analog or derivative thereof, or a pharmaceutically acceptable salt or ester thereof. The isolated cyclic peptide of claim 1 , wherein the peptide comprises: The isolated cyclic peptide of claim 1 , wherein at least one amino acid is a D-amino acid. The isolated cyclic peptide of claim 3 , wherein the N-terminal amino acid is a D-amino acid. The isolated cyclic peptide of claim 1 , wherein the N-terminal ring structure comprises a thioether linkage. The isolated cyclic peptide of claim 5 , wherein the thioether linkage is between an N-terminal acetyl group and a cysteine residue. The isolated cyclic peptide of claim 1 , wherein the peptide comprises a C-terminal amide. The isolated cyclic peptide of claim 1 , wherein the peptide comprises at least one N-methyl amide in the linear portion of the peptide. An isolated peptide comprising the amino acid sequence of SEQ ID NO: 7. An isolated peptide comprising any one of the peptides in Tables 2, 6, 8, or 9 or FIGS. 12A, 12B , or 21 . The isolated peptide of claim 1 , wherein the peptide inhibits activity of cofactor-independent phosphoglycerate mutase with an IC 50 of 100 μM or less. The isolated peptide of claim 11 , wherein the peptide inhibits activity of cofactor-independent phosphoglycerate mutase with an IC 50 of 1 pM to 100 μM. A pharmaceutical composition comprising the isolated peptide of claim 1 and a pharmaceutically acceptable carrier. A method of treating or inhibiting infection with an organism expressing at least one cofactor-independent phosphoglycerate mutase in a subject, comprising administering to the subject an effective amount of the isolated peptide of claim 1 . The method of claim 14 , wherein the subject is infected with an organism selected from the group consisting of a nematode, a trypanosome, a helminth, a protozoan parasite, or a bacterium. The method of claim 15 , wherein the subject is infected with a nematode, and the nematode comprises one or more of Brugia malayi, Brugia Wuchereria bancrofti, Onchocerca volvulus, Loa loa, Mansonella streptocerca, Mansonella perstans, Mansonella ozzardi, Dirofilaria immitis, Trichinella, Parafilaria bovicola, Onchocerca dermatan, Onchocerca ochengi, Onchocerca dukei, Stenofilaria assamensis , and Parafilaria multipapillosa. The method of claim 15 , wherein the subject is infected with a bacterium and the bacterium comprises one or more of Staphylococcus aureus, Bacillus anthracis, Streptococcus pneumoniae , and Escherichia coli. The method of claim 14 , wherein the peptide is administered orally, intravenously, or topically. The method of claim 14 , further comprising administering one or more of an antiparasitic or antibiotic agent to the subject. A method of treating or inhibiting infection with an organism expressing at least one cofactor-independent phosphoglycerate mutase in a subject, comprising administering to the subject an effective amount of the pharmaceutical composition of claim 13 .
CPC Classification	PEPTIDES Preparations For Medical; Dental Or Toiletry Purposes Specific Therapeutic Activity Of Chemical Compounds Or Medicinal Preparations Technologies For Adaptation To Climate Change
Extended Family	039-602-918-716-795 034-194-588-403-566 104-295-379-970-513 173-384-641-586-371 011-793-354-350-06X 007-946-306-676-540 059-392-424-913-230 039-872-212-072-545
Patent ID	20190169234
Inventor/Author	Inglese James Dranchak Patricia Macarthur Ryan Suga Hiroaki Yu Hao Carlow Clotilde Li Zhiru
IPC	C07K7/64 A61K38/12 A61K45/06 A61P33/10
Status	Active
Owner	The United States of America As Represented By The Secretary Department of Health and Human Services The University of Tokyo New England Biolabs Inc
Simple Family	039-602-918-716-795 034-194-588-403-566 173-384-641-586-371 104-295-379-970-513 011-793-354-350-06X 007-946-306-676-540 059-392-424-913-230 039-872-212-072-545
CPC (with Group)	C07K7/64 A61K38/00 A61K38/12 A61P33/10 C07K7/06 C07K7/08 C07K7/56 C07K14/00 Y02A50/30 A61K45/06
Issuing Authority	United States Patent and Trademark Office (USPTO)
Kind	Patent Application Publication