National Institutes of Health, a Component of the US Dept. of Health & Human Services

The United States of America As Represented by the Department of Health

Georgetown University

Peter P Roller

Larry K Keefer

Miki Akamatsu

C Richter King

Dajun Yang

Joseph E Saavedra

Feng-Di Lung

Johannes H Voigt

Joseph Saavedra

Ya-Qui Long

Ya-Qiu Long

Peng Li

The present disclosure concerns peptides and peptidomimetics having inhibitory activity against serine proteases. The disclosed peptides and peptidomimetics are particularly useful as selective inhibitors of matriptase and MTSP1. Pharmaceutical compositions comprising serine protease inhibitors and methods for administering the compositions also are disclosed.

Serine protease inhibitors

Redox-stable, non-phosphorylated cyclic peptide inhibitors of SH2 domain binding to target protein, conjugates thereof, compositions and methods of synthesis and use

A compound of formula:in which L is sulfur, sulfoxide, oxygen or methylene, and a compound of formula:in which (i) aais Adi and aais Glu or (ii) each of aaand aais Adi, L is sulfur, sulfoxide, oxygen or methylene, which compounds (and their conjugates) bind to an SH2 domain in a protein comprising an SH2 domain, are non-phosphorylated, are redox-stable in vivo, are characterized by an ICin vivo of less than about 4.0 &#x3bc;M with respect to the SH2 domain in Grb2, and, upon binding to the SH2 domain of Grb2, have a turn conformation. A conjugate comprising a compound as described above and a carrier agent, a composition comprising (i) a compound or a conjugate as described above and (ii) a carrier, a method of inhibiting binding of an SH2 domain in a protein comprising an SH2 domain to a target protein in an animal, wherein the SH2 domain is contacted with a target protein-binding inhibiting effective amount of a compound or a conjugate as described above, and a method of synthesizing such conjugates.

A polymeric composition capable of releasing nitric oxide under physiological conditions which includes a biopolymer, such as a peptide, polypeptide, protein, oligonucleotide or nucleic acid, to which is bound a nitric oxide-releasing N O functional group; pharmaceutical compositions comprising the polymeric composition; and methods of treating biological disorders in which dosage with nitric oxide is therapeutic.

Nitric oxide-releasing 1-&lsqb;(2-carboxylato)pyrrolidin-1-yl&rsqb; diazen-1-ium-1,2-diolates and composition comprising same

A polymeric composition capable of releasing nitric oxide under physiological conditions which includes a biopolymer, such as a peptide, polypeptide, protein, oligonucleotide or nucleic acid, to which is bound a nitric oxide-releasing N,O,functional group; pharmaceutical compositions comprising the polymeric composition; and methods of treating biological disorders in which dosage with nitric oxide is therapeutic.

Biopolymer-bound nitric oxide-releasing compositions, pharmaceutical compositions incorporating same and methods of treating biological disorders using same

A polymeric composition capable of releasing nitric oxide under physiological conditions which includes a biopolymer, such as a peptide, polypeptide, protein, oligonucleotide or nucleic acid, to which is bound a nitric oxide-releasing N.sub.2 O.sub.2.sup.- functional group; pharmaceutical compositions comprising the polymeric composition; and methods of treating biological disorders in which dosage with nitric oxide is therapeutic.

Biopolymer-bound nitric oxide-releasing compositions, pharmaceutical

Growing community of inventors

Rockville, MD, United States of America

Peter P Roller