The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.

The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.

Date of Patent:
Mar. 26, 2024

Filed:

Mar. 29, 2023
Applicants:

Seton Hall University, South Orange, NJ (US);

Rutgers, the State University of New Jersey, New Brunswick, NJ (US);

Inventors:

Gregory R. Wiedman, New Milford, NJ (US);

Robert J. Tancer, Montville, NJ (US);

Chaoyang Xue, Livingston, NJ (US);

Assignees:

Seton Hall University, South Orange, NJ (US);

Rutgers, The State University of New Jersey, New Brunswick, NJ (US);

Attorney:
Primary Examiner:
Int. Cl.
CPC ...
C07K 7/00 (2006.01); A61K 38/12 (2006.01); A61P 31/10 (2006.01); C07K 7/08 (2006.01);
U.S. Cl.
CPC ...
C07K 7/08 (2013.01); A61K 38/12 (2013.01); A61P 31/10 (2018.01);
Abstract

An antifungal peptide targeting P4-ATPase function is synthesized based on Cdc50 loop region to identify peptides sensitize caspofungin by blocking flippase function. It was found that myristylated peptides based on 'AS15 sequence' was effective at high concentrations. A modified peptide, “AW9-Ma” showed minimum inhibitory concentration (MIC) of 64 μg/mL against H99 wild type and fractional inhibitory concentration (FIC) index value of 0.5 when used with caspofungin. With the AW9-Ma peptide,wild type was highly sensitive to caspofungin with a MIC of 4 μg/mL, the same as cdc50Δ mutant. Further assays with flow cytometry showed inhibition of lipid flippase enzyme activity and significant accumulation of phosphatidylserine on the cell surface. It was confirmed that the peptide co-localized with mCherry-tagged P4-ATPase protein Apt1 in. Modification studies of AW9 sequence showed that two lysine residues on the peptide are likely responsible for interaction with P4-ATPasee critical for antifungal activity.


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