University of California

Amicrobe, Inc.

Centre National De La Recherche Scientifique

Universitë De Bordeaux

Institut Polytechnique De Bordeaux

Timothy J Deming

Miaoer Yu

Jarrod A Hanson

Michael D Wyrsta

Jungyeon Hwang

Scott A Curtin

Galen D Stucky

Bruce M Novak

Michael P Bevilacqua

Diego Benitez

Scott W Seidel

Yintao Sun

Andrew Nowak

Eric G Gharakhanian

Lucas Koziol

Michael V Sofroniew

Diego Bentitez

April Rose Rodriguez

Paul K Hansma

Jianjun Cheng

Michael Wong

Thomas G Mason

Daniel E Morse

Johannes H Kindt

Jennifer Cha

Connie B Chang

Henrik Birkedal

Michael H Bartl

Jan L Sumerel

Sara M Graves

Yan Ao

BingBing Song

Chu-Ya Yang

Jessica R Kramer

Elisabeth Béatrice Michèle Garanger

Sébastien Jean Marie Lecommandoux

Shanshan Zhang

Victor Z Sun

Eric P Holowka

Described herein are compositions comprising at least two diblock copolypeptides, wherein each copolypeptide has an ionic segment with the opposite charge from the other. The copolypeptides form β-sheet structured hydrogel assemblies via polyion complexation when mixed in aqueous media. As a result of their unique physical properties, the hydrogels are useful as cell suspension or cell culture media, in drug or cell delivery systems, in scaffolds for tissue repair, or as 3d-printable media.

Polyion complex polypeptide hydrogels and uses thereof

Disclosed herein are mixtures of triblock or pentablock copolypeptide hydrogels (DCH). These hydrogels possess improved mechanical properties, such as elasticity, that are synergistically increased over the individual component DCHs, to greater than would be expected for a linear combination of the components. Also disclosed herein are methods of making and using the triblock and pentablock copolypeptide hydrogels.

Compositions comprising tri- and penta-block synthetic copolypeptide hydrogels

Methodology was developed for transformation of methionine residues into homocysteine derivatives. Methionine residues can undergo alkylation reactions at low pH to yield sulfonium ions, which can then be selectively demethylated to give alkyl homocysteine residues. This process tolerates many functional groups.

Preparation of functional homocysteine residues in polypeptides and peptides

The present invention is directed to copolypeptide hydrogels (DCH) containing non-ionic hydrophilic residues (DCH), incorporation of thermoresponsive elements into DCH, to generate thermoresponsive DCH (DCH), and hydrogels that include a combination of DCHand DCH. The invention includes preparation, uses, compositions containing the hydrogels and methods of tuning the hydrogels. The hydrogels can be used to deliver an agent or cells to an organism.

Non-ionic and thermoresponsive diblock copolypeptide hydrogels for delivery of molecules and cells

The present invention concerns the use of a thioether alkylation process for modulating the lower critical solution temperature of an elastin-like polypeptide comprising at least one methionine residue. It also concerns derivatives of elastin-like polypeptides and their preparation process.

Derivatives of elastin-like polypeptides and uses thereof

Improved synthetic copolypeptide antimicrobials contain cationic amino acid residues and may be based on a blocky sequence. These antimicrobials show low mammalian toxicity and may undergo directed self-assembly. The inventive synthetic copolypeptides are useful in treatment of wounds and other infections.

Composition with high antimicrobial activity and low toxicity

Some embodiments of the invention involve methods for introduction of various functional groups onto polypeptides, peptides and proteins by alkylation of thioether (a.k.a. sulfide) groups by ring opening reactions, creating new compositions of matter that may be useful for medical therapeutic or diagnostic applications. The thioether groups may either be present in the polypeptides, or may be added to polypeptides by chemical modification, such as by alkylation of thiol (sulfhydryl) groups.

Polypeptides, peptides, and proteins functionalized by alkylation of thioether groups via ring-opening reactions

Methods for preparation of novel amphiphilic derivatives of thioether containing block copolypeptides with narrow chain length distributions are described. These block copolymers can be chemically modified by oxidation and alkylation of the thioether containing residues. These materials generate self-assembled micelles, vesicles and hydrogels, or emulsions with oil phases. These assemblies can be used to encapsulate and delivery therapeutic molecules. The assemblies can be taken up by cells to release molecules from the assemblies.

Amphiphilic derivatives of thioether containing block copolypeptides

Compositions and uses of materials with high antimicrobial activity and low toxicity

This invention relates, e.g., to a composition suitable for administration to the central nervous system (CNS), comprising a block copolypeptide hydrogel, which comprises a biologically active material that is mixed with the hydrogel or that is attached to the polypeptide chain of the hydrogel, wherein the composition is suitable for administration to the CNS. Also disclosed are methods of making and using compositions of the invention as depots or as scaffolds for cell migration, and pharmaceutical compositions and kits for implementing methods of the invention.

Synthetic diblock copolypeptide hydrogels for use in the central nervous system

An emulsion includes a substantially continuous liquid medium, and a plurality of droplet structures dispersed within the substantially continuous liquid medium. Each droplet structure of the plurality of droplet structures includes an outer droplet of a first liquid having an outer surface; an inner droplet of a second liquid having an inner surface contained within the outer surface of the outer droplet of the first liquid, the second liquid being immiscible in the first liquid, wherein the inner and outer droplets have a boundary surface region therebetween; an outer layer of block copolymers disposed on the outer surface of the outer droplet; and an inner layer of block copolymers disposed on the inner surface of the inner droplet. The block copolymers include a hydrophilic polymer block and a hydrophobic polymer block that act in combination to stabilize the droplet structure, and the first liquid is immiscible in the substantially continuous liquid medium.

Copolymer-stabilized emulsions

Methods and compositions for the generation of polypeptides having varied material properties are disclosed herein. Methods include means for initiating the polymerization of aminoacid-N-carboxyanhydride (NCA) monomer by combining the monomer with an amido-containing metallacycle, for making self assembling amphiphilic block copolypeptides and related protocols for adding oligo(ethyleneglycol) functionalized aminoacid-N-carboxyanhydrides (NCAs) to polyaminoacid chains. Additional methods include means of adding an end group to the carboxy terminus of a polyaminoacid chain by reacting an alloc-protected amino acid amide with a transition metal-donor ligand complex to forming an amido-amidate metallacycle for use in further polymerization reactions. Novel compositions for use in peptide synthesis and design including five and six membered amido-containing metallacycles and block copolypeptides are also disclosed.

Methods and compositions for controlled polypeptide synthesis

A design strategy for constructing hierarchically structured materials using nanoparticles and synthetic biopolymers has been developed. Block copolypeptides or homopolymer polyelectrolytes are used as structure-directing agents to arrange nanoparticles (composed of metals, metal non-oxides, metal oxides, or organics) into unusual microstructures, such as spheres, 'apples' and 'cups.' Hollow spheres can be made wherein nanoparticles of one composition are spatially oriented completely interior or exterior to nanoparticles of a second composition. These aggregates contain nanoparticles only in the shell walls, and maintain their hollowness upon calcination. These shapes can also be fabricated into films. These robust materials are anticipated to have great promise in applications that require surface catalysis, magnetic/electronic/optic properties, transport capabilities, and combinations thereof, such as drug delivery, packaging, catalysis, and sensors.

Nanoparticle assembled hollow spheres

A series of initiators based on transition metal complexes for the polymerization of optically active beta-lactams into poly-beta-peptides and block copolymers have been developed. These initiators are unique in being able to eliminate chain transfer and chain termination side reactions from these polymerizations resulting in narrow molecular weight distributions, molecular weight control, and the ability to prepare copolymers of defined block sequence and composition.

Transition metal initiators for controlled poly (beta-peptide) synthesis from beta-lactam monomers

Growing community of inventors

Summerland, CA, United States of America

Timothy J Deming