Harvard College

University of Pennsylvania

Beth Israel Deaconess Medical Center, Inc.

Wisconsin Alumni Research Foundation

The Scripps Research Institute

The Salk Institute for Biological Studies

Alan Saghatelian

Barbara B Kahn

E James Petersson

David R Liu

Samuel Helmer Gellman

Benjamin F Cravatt

Alan D Attie

Juan Pablo Maianti

Lisa M Johnson

Mark Patrick Keller

Ralph E Kleiner

Mark A Herman

Ismail Syed

Edwin Homan

Kyle P Chiang

Pedro M M Moraes Vieira

Mark M Yore

Sherry Niessen

Nadim Jessani

Arul Joseph

Mark M York

Pedro MM Moraes Vieira

The invention includes a thioamide-modified peptide, wherein the thioamide modification increases the in vivo half-life of the peptide. The invention further includes methods of treating or preventing a disease or disorder in a subject in need thereof, the method comprising administering to the subject a thioamide-modified peptide of the invention.

Thioamide-modified peptides and uses thereof

The invention provides, inter alia, fatty acyl hydroxy fatty acid (FAHFA; a novel class of estolide-related molecules) and diagnostic and treatment methods for a variety of disorders&#x2014;including diabetes-related disorders, Metabolic Syndrome, polycyctic ovarian syndrome, cancer, and inflammatory disorders&#x2014;using them; as well as methods of screening for additional compounds that are useful in treating these disorders and/or that modulate FAHFA levels, FAHFA-mediated signaling, and FAHFA-mediated biological effects.

Lipids that increase insulin sensitivity and methods of using the same

Provided herein are methods for treating type 1 diabetes and its sequelae (e.g., cardiovascular, renal or neurologic diseases for which type 1 diabetes is a risk factor) in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a fatty acid ester of a hydroxy fatty acid (FAHFA), or a pharmaceutically acceptable salt thereof.

Fatty acid esters of hydroxy fatty acids (FAHFAs) for use in the treatment of type 1 diabetes

Method of stabilizing a bioactive peptide against protease hydrolysis

Described herein are peptide analogs of glucagon-like peptide 1 (GLP-1) that retain agonist activity, but are more resistant to proteolytic degradation than native GLP-1. In the analogs, at least one &#x3b1;-amino acid found in the native GLP-1 is replaced with a &#x3b2;-amino acid residue, which may or may not be cyclically constrained. Pharmaceutical compositions containing the analogs are described, as are methods to treat diabetes, and methods to make proteolytically resistant GLP-1 analogs.

Alpha/beta-polypeptide analogs of glucagon-like peptide 1

The invention provides, inter alia, fatty acyl hydroxy fatty acid (FAHFA; a novel class of estolide-related molecules) and diagnostic and treatment methods for a variety of disorders&#x2014;including diabetes-related disorders, Metabolic Syndrome, polycystic ovarian syndrome, cancer, and inflammatory disorders&#x2014;using them; as well as methods of screening for additional compounds that are useful in treating these disorders and/or that modulate FAHFA levels, FAHFA-mediated signaling, and FAHFA-mediated biological effects.

Alpha/beta-polypeptide analogs of glucagon-like peptide-1

Macrocyclic compounds that specifically inhibit insulin degrading enzyme (IDE) are provided. Pharmaceutically acceptable salts, solvates, hydrates, stereoisomers, polymorphs, tautomers, isotopically enriched forms, and prodrugs of the macrocyclic IDE inhibitors are also described. Pharmaceutical compositions are also provided. In vivo and in vitro methods of using the IDE inhibitor, and pharmaceutical compositions comprising the IDE inhibitor, for example, for the inhibition of IDE in a subject exhibiting aberrant IDE activity, impaired insulin signaling, or insulin resistance, for example, a subject having diabetes, are also provided.

Macrocyclic insulin-degrading enzyme (IDE) inhibitors and uses thereof

A multidimensional profiling strategy that combines activity-based proteomics and metabolomics was used to determine that an active protein, which is a previously uncharacterized enzyme highly elevated in aggressive cancer cells, serves as a central node in an ether lipid signaling network that bridges platelet-activating factor and the lysophospholipids. Biochemical studies confirmed that the active protein regulates this pathway by hydrolyzing the metabolic intermediate 2-acetyl monoalkylglycerol. Inactivation of the active protein disrupted ether lipid metabolism in cancer cells and impaired cell migration and tumor growth in vivo.

Enzyme regulating ether lipid signaling pathways

Activity-based compositions for analyzing metalloproteases are disclosed, where the compositions include a chemical compound including a hydroxamate moiety and a benzophenone moiety. Methods for synthesizing these compounds are also disclosed, as well as methods of using them for determining the bioactivity of a compositions comprising active compounds toward a metalloproteases and for determining the potency of an inhibitor against a metalloprotease.

Proteomic analysis

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Somerville, MA, United States of America

Alan Saghatelian