Monsanto Company

G.d. Searle & Company

Feder, Joseph

Harakas, Nicholaos K.

Connolly, Daniel T.

Wittwer, Arthur J.

Schaumann, Jon P.

Arthur J Wittwer

Joseph Feder

Mihaly V Toth

Susan C Howard

Michael A Sanzo

Barry C Holwerda

Raymond A Dwek

Thomas William Rademacher

Daniel T Connolly

Raj B Parekh

Jon P Schaumann

Nicholaos K Harakas

Joseph K Welply

Jayne C Marasa

A class of compounds is described for use as fluorogenic substrates for herpesvirus proteases and for use in an assay to identify inhibitors of herpesvirus proteases. ##STR1## wherein W is selected from glycine, 4-aminobutyric acid, 5-aminopentanoic acid, 6-aminocaproic acid and 7-aminoheptanoic acid; wherein Y is selected from EDANS, Abz, DANSYL, nicotinic acid, 4-guanidino-benzoic acid, N-methyl-Abz, 4-chloro-Abz, 5-chloro-Abz, 6-chloro-Abz, 3,5-dibromo-Abz, 6-amino-nicotinic acid, 2-amino-nicotinic acid, 2-chloronicotinic acid, niflumic acid and fluorogenic derivatives thereof; and wherein Z is selected from tryptophan, tyrosine, phenylalanine, p-nitrophenylalanine, m-nitrophenylalanine, DABSYL, DABCYL and halogenated derivatives thereof.

Reagent and method for determining activity of herpes protease

A class of compounds is described for use as fluorogenic substrates for herpesvirus proteases and for use in an assay to identify inhibitors of herpesvirus proteases. Compounds of particular interest are defined by Formula II ##STR1## wherein W is selected from glycine, 4-aminobutyric acid, 5-aminopentanoic acid, 6-aminocaproic acid and 7-aminoheptanoic acid; wherein Y is selected from EDANS, Abz, DANSYL, nicotinic acid, 4-guanidino-benzoic acid, N-methyl-Abz, 4-chloro-Abz, 5-chloro-Abz, 6-chloro-Abz, 3,5-dibromo-Abz, 6-amino-nicotinic acid, 2-aminonicotinic acid, 2-chloronicotinic acid, niflumic acid and fluorogenic derivatives thereof; and wherein Z is selected from tryptophan, tyrosine, phenylalanine, p-nitrophenylalanine, m-nitrophenylalanine, DABSYL, DABCYL and halogenated derivatives thereof.

A novel and unique plasminogen activator inhibitor fragment is obtained from human umbilical vein endothelial cells which has the following characteristics:

Tissue plasminogen activator inhibitor and method of purification

Plasminogen activators (PA) are obtained from cultured normal human colon cells which are adaptable to large scale production. A purified tissue PA (t-PA) is obtained from CCD-18Co normal human colon fibroblast cells which shows chemical differences from Bowes melanoma t-PA.

Large scale production of plasminogen activator from normal human colon

A method of increasing the specific activity of tissue plasminogen activator is disclosed which comprises increasing the proportion of neutral oligosaccharides in the tissue plasminogen activator glycoprotein.

Method of increasing specific activity of t-PA

Novel peptide fragments of tissue plasminogen activator are described which have activity for inhibiting (a) the binding of tPA to human endothelial cells, and (b) the inactivation of tPA by plasminogen activator inhibitor-1 (PAI-1). Six peptides or peptide amides with these activities have the sequences, numbered according to the native protein:

Peptide fragments of tissue plasminogen activator

Normal human colon fibroblast tissue plasminogen activator is separated by lysine-Sepharose affinity chromatography into Types I and II glycoforms and characterized with respect to the relative incidence of each type of oligosaccharide comprising the respective Types I and II glycoforms.

Tissue plasminogen activator from normal human colon cells

The solubility of tissue plasminogen activator in aqueous solution is enhanced by incorporating therein arginine or a non-toxic salt of arginine in an amount effective to increase the solubility of the t-PA without substantially inhibiting its potential biological activity upon administration.

Growing community of inventors

Ellisville, MO, United States of America

Arthur J Wittwer