A61K49/0056

Therapeutic inhibitor for EBV-associated tumor with tailor responsive optical imaging
20170304284 · 2017-10-26 ·

This invention provides a nucleus-permeable small-molecule inhibitor, L.sub.2P.sub.4 (where L.sub.2 is 4-(4-(Diethylamino)styryl)-N-carboxymethylpyridinium chloride and P.sub.4 is an amino acid sequence comprising CAhxYFMVFGGRrRK and they were coupled through amide bond) and synthesis thereof, which effectively targets the dimerization interface of EBNA1, a critical process for the growth of EBVs and the associated tumors. The present invention also provides method of treating and imaging EBV-associated cancers.

Ocular detection of amyloid proteins

Described are methods for the detection, in the eye of an individual, of protein aggregates or other misfolded proteins associated with disease using peptide or peptide mimic probes that preferentially associate with the protein aggregates or misfolded proteins, which can be accomplished non-invasively.

SYNTHETIC SOMATOSTATIN RECEPTOR LIGANDS

Disclosed are Somatostatin receptor ligands comprising a peptide moiety, pharmaceutical compositions and uses thereof. Disclosed are also synthetic Somatostatin receptor ligands comprising a cyclic peptide moiety and an active agent moiety covalently bonded to the cyclic peptide moiety through a nitrogen atom of a side chain functional group of an internal residue of the cyclic peptide moiety, pharmaceutical compositions and uses thereof. Disclosed are also synthetic Somatostatin receptor ligands comprising a cyclic peptide moiety and a nanoparticle active agent moiety covalently bonded to the cyclic peptide moiety, pharmaceutical compositions and uses thereof.

CU(I)-CATALYZED AZIDE-ALKYNE CYCLOADDITIONS (CUAAC) LIGANDS AND METHODS FOR CARRYING OUT CU(I)-CATALYZED AZIDE-ALKYNE CYCLOADDITION REACTIONS

A Cu(I)-Catalyzed Azide-Alkyne Cycloadditions (CuAAC) ligand comprising: a catalytic core; a fluorous tag; and a linker binding the fluorous tag to the catalytic core. A method for carrying out a Cu(I)-Catalyzed Azide-Alkyne Cycloaddition reaction, comprising: combining in a solution an alkyne-tagged component, an azide-tagged component and a Cu(I)-Catalyzed Azide-Alkyne Cycloadditions (CuAAC) ligand comprising: a catalytic core; a fluorous tag; and a linker binding the fluorous tag to the catalytic core; filtering the solution through a solid phase extraction filter to remove Cu(I)-ligand catalyst and/or excess ligand.

Self-assembling complex for targeting chemical agents to cells
09789201 · 2017-10-17 · ·

The present invention relates to a complex that can be injected into the body to hone in on target cells to deliver molecules. In one embodiment, the invention provides a drug delivery system that includes components that self-assemble into one targeted conjugate. In another embodiment, the invention includes a targeted carrier protein and a nucleic acid sequence non-covalently linked to one or more drugs.

EGFL7 targeting and/or binding polypeptides and methods for inhibiting angiogenesis

Polypeptides that target and/or bind to EGFL7 or its receptor and thereby reduce EGFL7 pro-angiogenic activity are provided. In this way, the polypeptides are, in an aspect, useful in the treatment of diseases, disorders, or conditions that involve pathological angiogenesis, such as, for example, cancer.

Activatable membrane-interacting peptides and methods of use

The present disclosure provides activatable and detectable membrane-interacting peptides that, following activation, can interact with phospholipid bilayers, such as cell membranes. The present disclosure also provides methods of use of such compounds. The compounds of the present disclosure are of the general structure X.sup.1a-A-X.sup.2-Z-X.sup.1b, where A is a membrane-interacting peptide region having a plurality of nonpolar hydrophobic amino acid residues that, following separation from portions Z, is capable of interaction with a phospholipid bilayer; Z is an inhibitory peptide region that can inhibit the activity of portion A; X.sup.2 is a cleavable linker that can be cleaved to release cleavage products from the compound; and X.sup.1a and X.sup.1b are optionally-present chemical handles that facilitate conjugation of various cargo moieties to the compound. Prior to cleavage of the composition at X.sup.2, the composition acts as a promolecule that does not associate with cellular membranes to a significant or detectable level. Following cleavage at cleavable linker X.sup.2, the cleavage product including portion A is free to interact with a phospholipid bilayer (e.g., a cell membrane), and thus accumulate at a site associated with a cleavage-promoting environment. Detection of the membrane-associated cleavage product can be accomplished by detection of a moiety attached through X.sup.1a and/or X.sup.1b. Such compositions can be used in a variety of methods, including, for example, use in directly imaging active clotting within a subject.

GRP78 TARGETED CONJUGATES

Accordingly, certain embodiments of the invention provide a conjugate of formula (I): P-(X-D)n, wherein P is a peptide that binds to a glucose regulated protein 78 (GRP78); X is a direct bond or a linking group; D is a detectable agent; and n is 1 to 4. Certain embodiments of the invention provide a pharmaceutical composition comprising a conjugate of formula (I) and a pharmaceutically acceptable excipient. Certain embodiments of the invention provide a method for treating or preventing cancer in an animal (e.g., a human) comprising administering a therapeutically effective amount of a conjugate of formula (I) (e.g., a conjugate comprising a therapeutic radionuclide) to the animal.

Peptoid-based chelating ligands for selective metal chelation

The present disclosure provides peptoid-based chelating ligands, corresponding cyclic peptoids, and methods of making thereof. Functional groups may be tailored for high metal binding affinity and selectivity. The side chains of a cyclic peptoid according to the present disclosure may be selected based on, for example, high affinity for actinide or other metal ions, selectivity for actinide or other metal ions, the ability to recover a metal once it is bound to the peptoid, and whether the overall peptoid should be hydrophobic or hydrophilic. Unlike siderophores, peptoid-based chelating ligands of the present disclosure are not readily hydrolyzed under physiological conditions. Therefore, peptoid-based chelating ligands may be, for example, used to treat actinide (e.g., iron and lead) poisoning in vivo. Moreover, peptoid-based chelating ligands of the present disclosure may be used for medical imaging, chelation therapy, drug delivery, and separation technologies, for example.

Two-dimensional (2D) bismuth nanocomposite, and preparation method and use thereof

The disclosure relates to a two-dimensional (2D) bismuth nanocomposite, and a preparation method and use thereof, and belongs to the field of nanobiotechnology. The 2D bismuth nanocomposite of the disclosure is an ultra-thin bismuth nanosheet that is loaded with platinum nanoparticles and modified with indocyanine green (ICG) and surface targeting polypeptide Ang-2. The 2D bismuth nanocomposite Bi@Pt/ICG-Ang2 of the disclosure can not only realize the targeted photothermal and photodynamic combination therapy for tumors, but also realize the dual-mode imaging combining CT and fluorescence imaging.