Kansas State University Research Foundation

John M Tomich

Takeo Iwamoto

Bruce D Schultz

James R Broughman

Xiuzhi Susan Sun

Pinakin R Sukthankar

Sushanth Gudlur

Iwamoto Takeo

Luz Adriana Avila Flores

Sherry Fleming

Xinchun Shen

Gerald Reeck

Lawrence P Sullivan

Raman Chandrasekar

Yasuaki Hiromasa

Described herein are nucleic acid-peptide capsule complexes or nanoparticles comprising pre-formed peptide capsules and nucleic acids bound the exterior surface of the capsule, such that the wrap around the capsule membrane. The peptide capsules comprise bilayer membrane defining a liquid-receiving interior space and comprises a plurality of branched, amphipathic peptides. Method of making and using such complexes for delivering nucleic acids in vivo and in vitro are also described.

Nucleic acid-peptide capsule complexes

Described are nanoparticulates comprising a metallic nanoparticle core and a peptide coating or shell encapsulating the nanoparticle core and being covalently bonded thereto. The coating is formed from a plurality of branched, amphipathic peptides, each comprising a polar/positively charged C-terminal segment, a branch point, and two hydrophobic N-terminal segments extending from the branch point. Methods of forming and using the nanoparticulates are also described. When a plurality of first and second peptides are added sequentially to the nanoparticle core, the peptides they self-assemble to form an interlocking peptide network bilayer where the respective hydrophobic segments of the peptides form beta-sheet structures in which the opposed sequences interlock to form a zipper-like structure in three dimensions.

Multifunctional metallic nanoparticle-peptide bilayer complexes

Therapeutic peptides (and peptoids) for preventing or inhibiting tissue damage associated with ischemia and/or reperfusion are provided, along with peptides (and peptoids) for preventing or inhibiting cancerous tissue growth. The peptides are derived from &#x3b2;2-glycoprotein I. Pharmaceutical and veterinary compositions comprising the peptides are also provided. Methods of using the peptides to prevent or inhibit tissue damage associated with ischemia and/or reperfusion and/or to prevent or inhibit tissue damage or the growth of cancerous tissue are also provided.

&#x3b2;2-glycoprotein I peptide inhibitors

The present invention provides branched amphipathic peptides and vesicles formed thereof. The peptides comprise a polar/positively charged C-terminal segment, a branch point, and two hydrophobic N-terminal segments extending from the branch point. The vesicles are formed using a plurality of first and second peptides, wherein the first peptide has a different chain length from the second peptide. When a plurality of the first and second peptides are mixed together, they self-assemble to form small spheres defined by a membrane consisting of an interlocking peptide network bilayer and having a liquid-receiving interior space (i.e., hollow core). In the bi-layer, the respective hydrophobic segments of the peptides form beta-sheet structures having a hydrogen bond-stabilized, anti-parallel orientation in which the opposed sequences interlock to form a zipper-like structure in three dimensions. Thus, the peptide assembly (i.e., vesicle) can be held together at reduced concentrations where lipid vesicles would breakdown.

Branched amphipathic oligo-peptides that self-assemble into vesicles

The present invention provides a family of peptides based upon the M2GlyR sequence. These peptides are derivatives of the M2GlyR sequence and can be modified at their ends to include a plurality of polar amino acid residues to enhance their solubility. Particularly preferred derivatives include portions of the M2GlyR sequence which are palindromic to another portion of the peptide or to the M2GlyR sequence itself. Preferably these portions are at least 7 amino acid residues in length. Peptides embraced by the present invention are characterized by having greater effects on the transepithelial electrical resistance of cells at lower concentrations. Peptides of the present invention have been shown to increase Isc in MDCK epithelial cell monolayers with half maximal effects observed at or below 30 &#x3bc;M, a nearly 10-fold improvement over any peptide previously characterized in the M2GlyR family. Additionally, peptides of the invention have been shown to increase transepithelial electrical conductance and modulate the permeability of tight junctions in epithelial cells.

Channel forming peptides

A novel peptide adhesive motif is described that requires no receptor or cross-links to achieve maximal adhesive strength. Several peptides with different degrees of adhesive strength have been designed and synthesized using solid phase chemistries. All peptides contain a common hydrophobic core sequence flanked by positively or negatively charged amino acids sequences.

PH dependent adhesive peptides

Improved methods and preparations are provided for ocular administration of therapeutic drugs. The preparations include respective quantities of a drug and a peptide which enhances transport of the drug across ocular tissues. The drug and peptide components may be separately administered or used as a mixture. The preferred peptide is NC-1059 (SEQ. ID NO. 1).

Peptide-enhanced corneal drug delivery

The present invention provides a family of peptides based upon the M2GlyR sequence. These peptides are derivatives of the M2GlyR sequence and can be modified at their ends to include a plurality of polar amino acid residues to enhance their solubility. Particularly preferred derivatives include portions of the M2GlyR sequence which are palindromic to another portion of the peptide or to the M2GlyR sequence itself. Preferably these portions are at least 7 amino acid residues in length. Peptides embraced by the present invention are characterized by having greater effects on the transepithelial electrical resistance of cells at lower concentrations. Peptides of the present invention have been shown to increase Isc in MDCK epithelial cell monolayers with half maximal effects observed at or below 30 &mgr;M, a nearly 10-fold improvement over any peptide previously characterized in the M2GlyR family.

M2GlyR derived channel forming peptides

The present invention is directed to multiple-peptide channel assemblies for transport of anions such as chloride ions through epithelial cells, synthetic peptides capable of forming such channel assemblies and methods for using channel assemblies in therapeutic contexts for altering the flux of water across epithelial cells. The channel assemblies are composed of a plurality of peptides that transport through the membrane of an epithelial cell and provide for alteration of the flux of water through the cell. The peptides are soluble in water to a level of at least 10 mM and exhibit at least about 50% helical content when dispersed in a 40% trifluoroethanol/60% water solution. The peptides ideally have the amino acid sequence ABC(X).sub.n DEF, where A, B, C, D, F and X are individual amino acid residues, n ranges from 12-24 and at least one of the amino acids selected from the group consisting of A, B, and C is a charged amino acid, and at least one of the amino acids selected from the group consisting of D, E, and F is a charged amino acid. The method hereof provides for altering flux of water from an epithelial cell and includes providing from 3-6 peptides capable of forming a channel assembly with each of such peptides having from about 18-30 amino acid residues therein, then contacting the peptides with a surface of an epithelial cell to cause the peptides to embed therein and alter the flux of water across the cell.

Synthetic macromolecular channel assembly for transport of chloride ions

Methods for making preparations of homogenous peptides are disclosed. In these methods, reversible alterations of the physicochemical properties of the peptides are exploited. In preferred embodiments, the methods include the following sequential steps: (1) exhaustive capping is carried out during solid-phase synthesis of a desired peptide; (2) a cleavable linker is attached to the peptide, (3) a polymer is added to the peptide either by condensation with preformed polymer or by in situ polymerization such that the linker is interposed between the polymer moiety and the peptide moiety of the resultant adduct; alternatively, steps (2) and (3) can be conducted simultaneously by attaching a combination polymer/linker to the peptide; (4) the polymer-peptide adduct is cleaved from the resin; (5) the polymer-peptide adduct is purified from undesired, nonadducted peptides; and (6) the polymer-peptide adduct is cleaved at the linker, and the desired peptide is purified from the polymer. In some cases, it may be desirable to omit step (6) in order to leave the polymer moiety attached to the desired peptide. For example, the polymer-peptide adducts of the present invention are very soluble in water, and therefore can be used to solubilize amphipathic peptides. Additionally, the polymer moieties of the polymer-peptide adducts can elicit immune responses in mammals or birds; thus, the adducts and corresponding antibodies can be used in research protocols to track the peptide moieties of the adducts.

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Manhattan, KS, United States of America

John M Tomich