The United States of America, as Represented by the Secretary, Department of Health and Human Services

University System of Maryland

The United States Government as Represented by the Department of Veterans Affairs

Zoltan Szekely

Christopher J Michejda

Susan K Keay

Thomas P Conrads

Timothy D Veenstra

Marek W Cholody

Humcha Krishnamurthy Hariprakasha

Piotr Kaczmarek

A novel antiproliferative factor comprising a glycopeptide is disclosed. In specific embodiments, the novel antiproliferative factor is associated with the bladder. Compositions, diagnostic kits and reagents, and methods of using the compounds for identifying and/or treating interstitial cystitis and cancer are disclosed.

Antiproliferative factor and methods of use

Derivatives of a novel antiproliferative factor comprising a glycopeptide is disclosed. In specific embodiments, the novel antiproliferative factor is associated with the bladder. Compositions, diagnostic kits and reagents, and methods of using the compounds for identifying and/or treating interstitial cystitis and cancer are disclosed. In particular embodiments, the glycopeptide comprises D-proline.

Derivatives of APF and methods of use

Derivatives of bladder epithelial antiproliferative factor and methods of using them are disclosed. In specific embodiments, the glycopeptide compositions are useful for the treatment and/or prevention of medical conditions, including cancer. In other embodiments, there are compositions and methods related to treatment of bladder conditions. In particular embodiments, the glycopeptide comprises D-pipecolic acid or L-pipecolic acid.

A conjugate of formula: V&#x2014;(Y)&#x2014;Z-T: (I), T-X&#x2014;B&#x2014;(Y)&#x2014;Z-T': (II), V&#x2014;(Y)Z&#x2014;(Y&#x2032;)V&#x2032;: (III), T-X&#x2014;B&#x2014;(Y)&#x2014;Z&#x2014;(Y&#x2032;)&#x2014;X&#x2032;&#x2014;B&#x2032;-T&#x2032;: (IV), V&#x2014;(Y)&#x2014;Z&#x2014;(Y&#x2032;)&#x2014;X&#x2014;B-T: (V), V&#x2014;(Y)&#x2014;Z&#x2014;X&#x2014;B&#x2014;Z&#x2032;&#x2014;(Y&#x2032;)&#x2014;(V&#x2032;): (VI), or (W)&#x2014;(Y)&#x2014;[(Z)&#x2014;(Y&#x2032;)&#x2014;(X&#x2014;B)&#x2014;(Y&#x2033;)&#x2014;(Z&#x2032;)]&#x2014;(Y . . . )&#x2014;(W&#x2032;): (VII), in which W and W&#x2032; are independently a DNA intercalator or terminal subunit, V and V&#x2032; are independently a DNA intercalator, X and X&#x2032; are independently a DNA alkylator, B and B&#x2032; are the same or different and each is a heteoaromatic residue that is attached to the Nterminus of an alkylator subunit (X or X&#x2032;), Y, Y&#x2032;, Y&#x2033; and Y&#x2032;&#x2033; are independently a linker, T and T&#x2032; are independently terminal subunits, Z and Z&#x2032; are independently a polyamide group that binds to the minor groove of DNA, a, b, c, d, f, g, i, and j are independently 0 to 5, and e and h are independently 1 to 5, a composition comprising a conjugate of any of formulae (I)-(VII) and a carrier, and a method for treating cancer in a mammal comprising administering an effective amount of a conjugate of any of formulae (I)-(VII) or a composition comprising same.

Growing community of inventors

Gaithersburg, MD, United States of America

Zoltan Szekely