Southern Research Institute

The Uab Research Foundation

Cornell Research Foundation Inc.

Cornell University

The Penn State Research Foundation

H. Lee Moffitt Cancer Center and Research Institute, Inc.

Cornell Center for Technology, Enterprise and Commercialization

Steven Ealick

John A Secrist, Iii

Eric J Sorscher

William B Parker

Anthony E Pegg

Wayne Charles Guida

Shridhar Bale

Diane E McCloskey

The crystal structure of the complex of S-adenosylmethionine methyl ester with h&#x39b;doMetDC F223A, a mutant where the stacking of the aromatic rings of F7, adenine and F223 would be eliminated. The structure of this mutant with the ester shows that the ligand still maintains a syn conformation aided by pi-pi interactions to F7, hydrogen bonds to the backbone of Glu67, and electrostatic interactions. Several series of AdoMet substrate analogues with a variety of substituents at the 8 position of adenine were synthesized and analyzed for their ability to inhibit hAdoMetDC. To understand these results, virtual modeling of the enzyme inhibitor complexes and the crystal structures of human AdoMetDC with 5'-deoxy-5&#x2032;-[N-methyl-N-[2-(aminooxy)ethyl]amino-8-methyl]adenosine (MAOEMA) and 5&#x2032;-deoxy-5&#x2032;-[N-methyl-N-[4-(aminooxy)butyl]amino-8-ethyl]adenosine (MAOBEA) at the active site have been determined experimentally.

5',-substituted adenosynes preparation thereof and use as inhibitors of S-adenosylmethionine decarboxylase

A host cell stably transformed or transfected by a vector including a DNA sequence encoding for mutant purine nucleoside cleavage enzymes is provided. The transformed or transfected host cell can be used in combination with a purine substrate to treat tumor cells and/or virally infected cells. A nucleotide sequence encoding mutantderived purine nucleoside phosphorylase proteins which can be used in conjunction with an appropriate substrate to produce toxins which impair abnormal cell growth is also provided. A method is detailed for the delivery of toxin by generation within target cells or by administration and delivery to the cells from without. Novel purine nucleosides are detailed that yield a cytotoxic purine upon enzymatic cleavage. A synthetic process for nucleosides is also detailed.

Mutant purine nucleoside phosphorylase proteins and cellular delivery thereof

The present invention provides a procaryotic host cell stably transformed or transfected by a vector including a DNA sequence encoding for mutant purine nucleoside phosphorylase or hydrolase. The transformed or transfected procaryotic host cell can be used in combination with a purine substrate to treat tumor cells and/or virally infected cells. The present invention provides nucleotide sequences encoding mutantderived purine nucleoside phosphorylase proteins which can be used in conjunction with an appropriate substrate to produce toxins which impair abnormal cell growth. The invention provides for delivery of the toxin by generation within target cells or by administration and delivery to the cells from without.

Growing community of inventors

Ithaca, NY, United States of America

Steven Ealick