Wisconsin Alumni Research Foundation

Massachusetts Institute of Technology

The Penn State Research Foundation

Other

University of California

Quintessence Biosciences, Inc.

Mahidol University

Novagen, Inc.

Ronald Thaddeus Raines

Thomas J Rutkoski

Matthew B Soellner

Julie C Mitchell

George N Phillips, Jr

R Jeremy Johnson

Jason G McCoy

Laura Lee Kiessling

Jonathan Allen Hodges

Stephen M Fuchs

Ismet Tanrikulu

Kalie Mix

David M Lynn

Matthew D Shoulders

John Lukesh

Bradley L Nilsson

Nicholas McGrath

Joseph Bartholomew Binder

Michael Palte

Yi He

Ronald Jay Hinklin

Alan D Attie

Mark Gray-Keller

Timothy E Glass

Luke D Lavis

Brian James Graham

Trish Hoang

John C Lukesh, Iii

Sunil S Chandran

Brian Gold

Mary E Rabaglia

Eddie Leonard Myers

Bryan D Smith

Nile S Abularrage

Samuel Helmer Gellman

John A Kink

Laura Strong

Michael A Gelman

Leonard A Levin

James Vasta

Christopher M Jewell

Judith E Kimble

Naoki Umezawa

Matthew Allen

Jesús M Dones

Thomas P Smith

Annie Tam

Ian Windsor

Peter A Leland

L Lane Schultz

Stephen B Del Cardayre

Kristen A Andersen

Gregory Ellis

Benjamin Caes

Brett VanVeller

Lisa C Friedman

Terra Potocky

Parit Plainkum

Matthew Aronoff

Frank W Kotch

Ryan M Flessner

Jeet Kalia

Joseph B Binder

Laura E Strong

The present disclosure provides compositions, methods and kits for the treatment of cancer. Particularly, the present disclosure provides synergistic compositions comprising at least one cytotoxic ribonuclease and at least one MAPK-pathway inhibitor.

Combination chemotherapy for the treatment of cancer

Disclosed herein are circular zymogens of RNase 1 that have a proteolytic cleavage site and are activated by a specific protease. These circular zymogens are useful for treatment of disorders that are characterized by a specific protease (e.g., HTV-1 protease).

Circular strained zymogen compositions and methods of use

Novel synthetic human scale collagen triple helices assemblies are disclosed. Methods of making self-assembling collagen mimetic peptides that self-assemble into human scale collagen are also disclosed.

Method for the design of fibrillar collagen-mimetic peptide self-assemblies

Methods and reagents for esterification of biological molecules including proteins, polypeptides and peptides. Diazo compounds of formula I: where R is hydrogen, an alkyl, an alkenyl or an alkynyl, Rrepresents 1-5 substituents on the indicated phenyl ring and Ris an organic group. Rincludes a label, a cell penetrating group, a cell targeting group, or a reactive group or latent reactive group for reaction to bond to a label, a cell penetrating group, or a cell targeting group, among other organic groups useful for esterification of biological molecules. Also provided are diazo compounds which are bifunctional and trifunctional coupling reagents as well as reagents for the synthesis of compounds of formula I.

Reagents and methods for esterification

A method for esterification of one or more carboxylic acid groups in a compound containing one or more carboxylic acid groups wherein the esterification reagent is a diazo-compound of formula: wherein the Rand Rgroups of the diazo compound are selected such that the corresponding organic compound of formula: exhibits a —C—H pKa value between 18 and 29 as measured in DMSO. Specific reagents and methods for esterification are provided. The esterification reagents provided exhibit high selectivity for esterification of carboxylic acid groups over reaction with amine, alcohol or thiol groups in the compound containing one or more carboxylic acid groups. The method can be used to selectively esterify carboxylic acid groups in peptides or proteins.

Provided herein are dibenzocyclooctyne compounds useful as reagents in 1,3-dipolar cycloaddition reactions, and methods for their preparation.

Cyclooctynes for click chemistry

Dithioamine reducing agents useful for the reduction of disulfide bonds. The reducing agents of this invention are useful, for example, to reduce disulfide bonds, particularly in proteins, or to prevent the formation of disulfide bonds, particularly in proteins and other biological molecules. Reducing agents of this invention can be employed to regulate protein function in proteins in which a sulfhydryl group is associated with biological activity. Reducing agents of this invention can prevent inactivation of a given protein or enhance activation of a given protein or other biological molecule in vitro and/or in vivo. Reducing agents of this invention can prevent or reduce oxidation of cysteine residues in proteins and prevent the formation of reduced activity protein dimers (or other oligomers). Reducing agents of this invention are useful and suitable for application in a variety of biological applications, particularly as research and synthetic reagents. The invention provides S-acylated dithioamines which can be selectively activated reducing agents by removal of the S-acyl groups enzymatically or chemically. The invention further provides dithiane precursors of thioamino reducing agents. The invention provides dithioamine reducing agents, S-acylated dithioamines and dithianes which are immobilized on surfaces, including among others, glass, quartz, microparticles, nanoparticles and resins.

Dithioamine reducing agents

Novel collagen mimics are disclosed with a tripeptide unit having the formula (Xaa-Yaa-Gly), where one of the positions Xaa or Yaa is a bulky, non-electron withdrawing proline derivative. By substituting a proline derivative at either the Xaa or Yaa position in the native collagen helix, the stability of the helix is increased due solely to steric effects relative to prior known collagen-related triple helices. Methods are also disclosed for making the novel collagen mimics.

Collagen mimics

A method for esterification of one or more carboxylic acid groups in a compound containing one or more carboxylic acid groups wherein the esterification reagent is a diazo-compound of formula: wherein the Rand Rgroups of the diazo compound are selected such that the corresponding organic compound of formula: exhibits a &#x2014;C&#x2014;H pKa value between 18 and 29 as measured in DMSO. Specific reagents and methods for esterification are provided. The esterification reagents provided exhibit high selectivity for esterification of carboxylic acid groups over reaction with amine, alcohol or thiol groups in the compound containing one or more carboxylic acid groups. The method can be used to selectively esterify carboxylic acid groups in peptides or proteins.

Novel collagen-mimetic peptides are disclosed comprising the formula (Xaa-Yaa-Gly), where the amino acid at one of the Xaa positions is substituted with a homocysteine residue. Also disclosed are multi-stranded novel collagen-mimetic peptides comprising a first strand as described above that is covalently bonded with a disulfide bridge to a second strand comprising the formula (Xaa-Yaa-Gly), where the amino acid at one of the Yaa positions is substituted with a cysteine residue. Disulfide formation between the terminal thiol sulfur of the homocysteine residue of the first strand and the terminal thiol sulfur of the cysteine residue of the second strand reveals unstrained bridges that enhance the structure and substantially improve the stability of collagen triple helices as compared to other possible disulfide or thioether bridges. Thus, the disclosed collagen mimetic peptides have improved stability, and can be used to produce optimized collagen-like fibrillar assemblies for wound healing and other biomedical applications.

Optimal interstrand bridge for collagen mimics

Growing community of inventors

Madison, WI, United States of America

Ronald Thaddeus Raines