Brandeis University

The Hong Kong University of Science and Technology

Massachusetts Institute of Technology

USA As Represented by Secretary of the Navy

Children's Medical Center Corporation

Brandels University

Bing Xu

Yi Kuang

Huaimin Wang

Ian W Hunter

Timothy Manning Swager

Anthony Edward Pullen

Matthew Ming Fai Yuen

Peter G Madden

John Madden

Cheng Yang

Yuan Gao

Hongjian He

Ye Zhang

Hsiao-Hua Yu

Patrick A Anquetil

Ping Gao

Hongbo R Luo

Xuewen Du

Jie Zhou

Kit Ying Wong

Zhimou Yang

Keming Xu

Junfeng Shi

Pak Leung Ho

Hongwei Gu

Fan Zhao

Jingyu Li

Disclosed are peptides capable of enzymatically-induced self-assembly to which is conjugated a redox modulator. These peptides are enzymatically responsive hydrogelators, and they can be used to form pericellular hydrogels/nanofibrils upon exposure to target cells that secrete or express a surface bound ectoenzyme having hydrolase activity suitable to induce peptide gelation. These materials, and compositions containing the same, can be used for inhibiting cancer cell migration, inhibiting cancer cell survival, and/or inhibiting cancer cell growth.

Enzymatically activatable peptide-redox modulator conjugates and use thereof

Disclosed are a peptide capable of induced self-assembly by a bioactive molecule comprising a (i) hydrogelation-promoting amino acid sequence and (ii) an oligomerization sequence; compositions containing the peptide and, optionally, bioactive molecule; hydrogels formed thereby; and various methods of using the same.

Rapid formation of supramolecular hydrogels by short peptide and bioactive small molecules

The present invention relates to a branched peptide that includes a first peptide chain and a second peptide chain having its C-terminal amino acid covalently linked to a sidechain of an amino acid residue of the first peptide chain, wherein the first peptide chain includes a plurality of aromatic amino acids and, optionally, an aromatic group linked to an amino terminus of the first peptide chain; and the second peptide chain includes a plurality of hydrophilic amino acids and an enzyme cleavage site. Pharmaceutical compositions containing the branched peptide and one or more therapeutic agents in an aqueous medium are disclosed, where the branched peptides form micelle structures in the aqueous medium. Methods of using the pharmaceutical composition to deliver therapeutic agents, and for treating various disease conditions are also described.

Branched peptides for enzymatic assembly and mitochondria drug delivery

Disclosed are peptides that contain up to about 35 amino acids, including a plurality of aromatic amino acid residues and either (i) an amino acid residue that is phosphorylated or sulfated, or (ii) an amino acid comprising an ester-moiety linked via peptide bond, or both (i) and (ii), wherein the peptide is capable of self-assembly to form nanofibrils in the presence of an enzyme that hydrolyzes the phosphate group, the sulfate group, or the ester-moiety. These peptides are enzymatically responsive hydrogelators, and they can be used to form pericellular hydrogels/nanofibrils upon exposure to target cells that secrete or express a surface bound ectoenzyme having hydrolase activity suitable to induce peptide gelation. These materials, and compositions containing the same, can be used for in vitro and in vivo cellular imaging, treating cancerous conditions, collecting a secretome from a cell upon which the pericellular hydrogels/nanofibrils form, and screening the collected secretome.

Synthetic peptides, enzymatic formation of pericellular hydrogels/nanofibrils, and methods of use

This invention relates to a conjugate of formula (I): (A-Z-)-Q-Z-D (I), wherein Z, Z, Q, A, D, and n are as described herein. This invention also relates to a pharmaceutical composition including a pharmaceutically acceptable carrier and a conjugate of formula (I). This invention also relates to a method making a conjugate of formula (I), and the use of the conjugate for treating cancerous conditions, modulating cell membrane microheterogeneity, stimulating an immunoresponse, and forming a network on or near the inner or outer surface of target cells.

Amino acid- and peptide-steroid conjugates and use thereof

The invention relates to an enzymatically responsive product that includes an amino acid residue conjugated to a magnetic particle, wherein the amino acid residue is phosphorylated or sulfated or comprises an ester-moiety linked via peptide bond. Compositions containing the enzymatically responsive product, and the use thereof for separating distinct types of mammalian cells (e.g., cancer cells from normal cells), for treating a cancerous condition, and imaging cancer cells are also disclosed.

Enzymatically responsive magnetic particles and their use

The present technology relates to a polymeric material including a plurality of polymer subunits and an active cross-linker, wherein the active cross-linker is covalently linked to the plurality of polymer subunits. The active cross-linker offers a key building block for constructing novel molecular architecture in chemomechanical soft materials and illustrates a new approach to tailor material properties.

Polymeric materials having active cross-linkers, methods for making them, and use thereof

Disclosed herein are fibrillar molecular aggregates, which are morphologically and phenotypically similar to oligomers of aberrant proteins. The molecular aggregates, formed by self-assembly of small hydrophobic molecules, prevent the growth of microtubules. This unprecedented mechanism of 'self-assembly to interfere with self-organization' allows inhibition of the growth of cancer cells.

Inhibition of tumor growth with aggregates of small molecules

The invention relates to the application of peptides that can self-assemble to form supramolecular nanofibrils and hydrogels, hydrogel compositions containing the self-assembled supramolecular nanofibrils, and methods of uses and making the hydrogel compositions.

Supramolecular hydrogel of fMLF-based molecules and use thereof

Disclosed are nucleopeptide compounds that include a nucleobase, and an amino acid. Certain compounds further comprise a glycoside. The compounds may self-assemble to form supramolecular hydrogels. Also, the compounds may be used as a platform to examine specific biological functions (e.g., binding to DNA and RNA) of a dynamic supramolecular system that is able to interact with both proteins and nucleic acids. Other uses include: methods of growing cells and methods of delivering a substance to a cell.

Supramolecular nanofibers and hydrogels based on nucleic acids functionalized with nucleobases

Disclosed is a general methodology to create nanofibers of therapeutic molecules that have a dual role, as both the delivery vehicle and the drug itself. It is shown that with proper molecular design, the integration of enzymatic reaction and self-assembly provides a powerful method to create molecular hydrogels of clinically-used therapeutics without compromising their bioactivities. In addition, the results disclosed herein demonstrate enzyme-instructed self-assembly as a facile strategy for generating the supramolecular hydrogels of molecules that inherently have poor solubility in water. For example, by covalently connecting paclitaxel with a motif that is prone to self-assemble, a hydrogel of paclitaxel can be formed without compromising the activity of the paclitaxel.

Antineoplastic hydrogels, and enzyme-instructed preparations thereof

Disclosed is a general methodology to create nano fibers of therapeutic molecules that have a dual role, as both the delivery vehicle and the drug itself. It is shown that with proper molecular design, the integration of enzymatic reaction and self-assembly provides a powerful method to create molecular hydrogels of clinically-used therapeutics without compromising their bioactivities. In addition, the results disclosed herein demonstrate enzyme-instructed self-assembly as a facile strategy for generating the supramolecular hydrogels of molecules that inherently have poor solubility in water. For example, by covalently connecting paclitaxel with a motif that is prone to self-assemble, a hydrogel of paclitaxel can be formed without compromising the activity of the paclitaxel.

An adhesion bond between a metallic surface layer and a second surface is formed by treating the layers with a material comprising sulphur-containing molecules. The sulphur-containing molecules are applied as a surface treatment of the surfaces, so that the sulphur-containing molecules act as a coupling agent to bond chemically to both substrates form nanometer-sized structures on the surfaces. The nanometer-sized structures are incorporated into a self-assembly interlayer in between the surfaces, with the interlayer forming a bond to both surfaces.

Growing community of inventors

Newton, MA, United States of America

Bing Xu