The Uab Research Foundation

Other

The University of Alabama

Texas Tech University System

Virtual Drug Development, Inc.

Christie G Brouillette

Lawrence James DeLucas

Wayne J Brouillette

Donald D Muccio

Laurent Schmitt

Sadanandan Velu

Mark J Jedrzejas

Yancho Devedjiev

Jose Gabriel Garcia

Walter Cristofoli

John Christopher Kappes

Zhengrong Yang

Ina L Urbatsch

Yong-Chul Kim

Liyuan Mou

Sadanadan E Velu

R Stephen Porter

The present invention is directed to modified CFTR proteins or fragments thereof that contain single or multiple amino acid mutations to improve the structural stability of such CFTR proteins and/or fragments. Specifically, the modified CFTR proteins or fragment thereof differ from the wild-type human CFTR protein or fragment thereof by the presence of four or more mutations selected from V150D, M470V, S492P, F494N, S495P, A534P, I539T, G550E, G551D, R553Q, R555K, Q637R, S1255L, K1334G, S1359A, E1371Q, H1402S, Q1411D, and any combination thereof, such that the stability of the polypeptide is increased relative to that of the wild-type human CFTR polypeptide or fragment thereof.

Modified cystic fibrosis transmembrane conductance regulator (CFTR) polypeptides with increased stability and uses thereof

Disclosed are compounds that inhibit the microbial NAD synthetase enzyme. For example, disclosed are compounds of the formula Ar&#x2014;X&#x2014;Ar&#x2014;Y&#x2014;L&#x2014;Z&#x2014;Q, wherein Q is QAror ArQ; Ar, Ar, and Arare independently aryl or heteroaryl, optionally substituted with one or more substituents; X, Y, and Z are independently selected from the group consisting of a covalent bond or groups containing one or more of C, H, N, O, S atoms; L is a linker and Qis an alkylenyl, alkylenyl carbonyloxy alkyl, or alkylenyl carbonylamino alkyl group, optionally having a substituent; a covalent bond; a group containing amidine or guanidine function wherein the amidine or guanidine may be optionally N-substituted with an alkyl; or a zwitterion; or a pharmaceutically acceptable salt thereof. Also disclosed are methods which involve the use of the compounds of the present invention, for example, in treating or preventing a microbial infection in a mammal or plant, killing a prokaryote or decreasing prokaryotic growth, disinfecting a material or environment contaminated by a microbe, increasing food animal production, controlling harm to plants by a pest or insect, and combating agroterrorism. Examples of microbes affected by the compounds of the present invention are bacteria and fungi.

NAD synthetase inhibitors and uses thereof

The present invention provides methods of synthesizing and screening inhibitors of bacterial NAD synthetase enzyme, compounds thereof, and methods of treating bacterial and microbial infections with inhibitors of bacterial NAD synthetase enzyme.

Inhibitors of bacterial NAD synthetase

The present invention provides methods of treating or preventing fungal infections in a host comprising administering a treatment effective or treatment effective amount of a yeast NAD synthetase inhibitor compound. The invention further provides a method of killing yeast comprising administering a yeast NAD synthetase compound that selectively binds to catalytic sites in yeast whereby the yeast is killed.

Methods of treating fungal infections with inhibitors of NAD synthetase enzyme

Growing community of inventors

Birmingham, AL, United States of America

Christie G Brouillette