Yale University

University of Rhode Island

Board of Governors for Higher Education, State of Rhode Island and Providence Plantations

Rhode Island Council on Postsecondary Education (Statutory Successor to Rhode Island Board of Governors for Higher Education)

Other

Rhode Island Board of Governors for Higher Education

Oleg A Andreev

Yana K Reshetnyak

Donald M Engelman

Anna Moshnikova

Ursula Lehnert

Keykavous Parang

John Deacon

Donald M Engelmann

The invention features a composition comprising an immuno-stimulatory compound and a pHLIP® peptide, e.g., an immunostimulatory compound that comprises a cyclic purine dinucleotide, which binds to a stimulator of interferon genes (STING) such as a cGAMP cyclic compound inside a cell.

pHLIP®-mediated intracellular delivery of immuno-stimulatory compounds

The present subject matter provides compounds, compositions, and methods for identifying, monitoring, treating, and removing diseased tissue. Compounds, compositions, and methods for identifying, monitoring, and detecting circulating fluids such as blood are also provided.

Fluorescent compound comprising a fluorophore conjugated to a pH-triggered polypeptide

The invention features methods and compositions for eliciting an anti-tumor response in a subject comprising administering to the subject a pHLIPconstruct comprising an antibody recruiting molecule linked to one or more pHLIPpeptides by a non-cleavable linker compound. The construct increases the amount of the antibody recruiting molecule on the surface of a diseased cell.

pH-triggered membrane peptide-mediated epitope tethering at cell surfaces

The invention features a composition comprising a potent cytotoxic compound and a pH low insertion peptide, where, e.g., the cytotoxic compound cannot be used alone due to a lack of targeting. The pH low insertion peptide targets cytotoxic compounds to acidic diseased tissue, translocates cytotoxic compounds across plasma membranes into the cytosols of cells in acidic diseased tissues and induces cell death predominantly in the targeted acidic diseased tissue.

pH low insertion peptide targeted delivery of potent cytotoxic compounds

The present application relates to compositions comprising and methods of using a liposome comprising a pHLIP polypeptide, wherein a lipid bilayer of the liposome is substantially free of the pHLIP polypeptide.

Liposome compositions and methods of use thereof

Method of detecting diseased or damaged tissue with a pH-triggered polypeptide fluorophore composition

The present subject matter provides pH triggered peptides, as well as compositions methods, devices, and systems comprising the same. The pH triggered peptides include cyclic and short linear peptides, and may have higher affinity to a membrane lipid bilayer at low pH than at neutral or high pH.

pH-sensitive cyclic peptides

The invention features a compositions and methods for inducing an immune response to targeted cells. The compositions induce targeting of a cell by positioning carbohydrate epitopes on the surface of the cell by conjugation of the epitope to a pH-triggered membrane peptide (pHLIP&#xae;).

Carbohydrate tethering at cell surfaces to induce immune response

An environmentally sensitive membrane binding polypeptide, pH (low)-sensitive membrane peptide (pHLIP) has improved insertion kinetics balanced with solubility to selectively target acidic tissues.

Environmentally sensitive compositions comprising a pH-triggered membrane protein and methods of use thereof in the treatment and diagnosis of tumors

Liposome structures and methods of use thereof

Environmentally sensitive compositions and methods of use thereof

A polypeptide with a predominantly hydrophobic sequence long enough to span a membrane lipid bilayer as a transmembrane helix (TM) and comprising one or more dissociable groups inserts across a membrane spontaneously in a pH-dependant fashion placing one terminus inside cell. The polypeptide conjugated with various functional moieties delivers and accumulates them at cell membrane with low extracellular pH. The functional moiety conjugated with polypeptide terminus placed inside cell are translocated through the cell membrane in cytosol. The peptide and its variants or non-peptide analogs can be used to deliver therapeutic, prophylactic, diagnostic, imaging, gene regulation, cell regulation, or immunologic agents to or inside of cells in vitro or in vivo in tissue at low extracellular pH.

Growing community of inventors

South Kingstown, RI, United States of America

Oleg A Andreev