Emory University

The United States of America As Represented by the Secretary of

Alfred H Merrill, Jr

Dennis C Liotta

Ronald T Riley

Elaine W Wang

Joseph M Kinkade, Jr

Victoria L Stevens

Lisa Warden

Thomas E Keane

Kapil N Bhalla

Eva M Schmelz

Compositions, methods of use, isolation and biosynthesis of diimino-piperazine derivatives useful for the modification of sphingolipid metabolism and other biological functions are described. The preferred derivative is 2,6-bis-(&ohgr;-aminobutyl)-3,5-diimino-piperazine. This is a naturally occurring biochemical compound isolated from cells. The diimino-piperazine derivatives are useful as therapeutic agents when administered to patients to treat diseases and disorders involving cell regulation.

Diimino compounds for use as modulators of cell regulation

This invention provides a method of altering the metabolism of sphingolipids in a cell comprising contacting the cell with a fumonisin, or an analog thereof. The invention also provides a method of detecting the consumption of a fumonisin or a fumonisin analog in a subject comprising (A) detecting, in a sample from the subject, the state of the metabolic pathway of sphingolipids and (B) comparing the state of the metabolic pathway to that of a normal subject, the presence of a change in the state of the metabolic pathway indicating the consumption of a fumonisin or a fumonisin analog. Also provided is a method of detecting the presence of a fumonisin or fumonisin analog contamination in a sample from a food or feed comprising detecting a reaction of the metabolic pathway of sphingolipids, the presence of the reaction indicating the presence of a fumonisin or fumonisin analog contamination. Furthermore, novel fumonisin analogs and compositions comprising fumonisins and fumonisin analogs are provided.

Method of altering sphingolipid metabolism and detecting fumonisin ingestion and contamination

Sphingolipid derivatives and their methods of use

Diimino-piperazine derivatives for use as modulators of cell regulation

Method of altering sphingolipid metabolism and detecting fumonisin

A method and composition for enhancing biological response modifiers, such as promoting cellular differentiation, by using a Vitamin A or an analog thereof and sphingosine or an analog thereof.

Method of modifying cellular differentiation and function and

A method and composition for enhancing the action of biological response modifiers, such as promoting cellular differentiation, by using Vitamin A or an analog thereof and sphingosine or an analog thereof.

A method of preparing a substituted derivative of sphingosine comprising the steps of reducing serine methyl ester by a hydride reagent to form an aldehyde or aldehyde derivative, adding acetylide anions to the aldehyde to form an erythro-isomer or propargyl alcohol and inverting the propargyl alcohol by S.sub.N 2 inversion to form a threo-isomer. Either isomer can then be deprotected to form an alkyne with a 2-aminopropane 1,3-diol head group; this alkyne can be reduced to form sphingosine or a sphingosine derivitive which can be functionalized at the 4 and 5 positions to form a substituted derivative of sphingosine.

Growing community of inventors

Stone Mountain, GA, United States of America

Alfred H Merrill, Jr