Anja Schuster

Molecular cloning and characterization of a novel SH3 protein (SLY) preferentially expressed in lymphoid cells

A novel full-length cDNA was isolated from a murine T-cell lymphoma library that has an open reading frame encoding 381 amino acids. The predicted protein (termed SLY) contains a Src homology 3 domain and a sterile alpha motif, suggesting that it functions as a signaling adaptor protein in lymphocytes. Northern blot and in situ hybridization analysis showed a preferential expression in lymphoid tissues. The sly gene is located on the X-chromosome in close proximity to genes involved in various immune disorders. This is consistent with an additional role of SLY in immune pathology.

Cellular solid-phase binding assay and mass spectrometry for screening of α4β7 integrin antagonists

Abstract A qualitative cellular solid-phase binding assay for screening α4β7 integrin antagonists attached via photolinker to TentaGel® Macrobeads has been developed. An activation of the integrins with Mn 2+ was necessary to achieve binding to the bead bound antagonists. The identification of the resin bound compounds was done by mass spectrometry.

Synthesis and NMR Structure of Peptidomimetic α4β7-Integrin Antagonists

The development of new anti-inflammatory drugs is currently one of the great challenges in medicinal chemistry. Recently, 4 1and 4 7 integrins were shown to be promising targets for treating inflammatory and autoimmune diseases. 4 7 integrins bind to the mucosal addressin cell adhesion molecule 1 (MAdCAM-1) through their Leu-Asp-Thr sequence (LDT sequence) specifically and with high affinity. 6] An overexpression of MAdCAM-1 occurs in mouse models of colitis, in human inflammatory bowel disease (IBD), and in chronic inflammatory liver disease. 8] Recently, we and others were able to derive peptidic 4 7 integrin antagonists from the natural LDT-binding sequence. For the further development of nonpeptidic and highly selective drugs, we identified the structural and functional requirements of the LDT recognition sequence within 4 7 integrin antagonists by using several peptidomimetic variations such as peptoids, azapeptides, and reduced amide bonds (Scheme 1). An aromatic residue N-terminal to the LDTsequence

β-D-Mannose Based Peptidomimetics in the Design of α4ß1 and α4β7 Antagonists

Interfering protein-protein interaction by small non-peptidic molecules is one of the great challenges in medicinal chemistry. The use of rigid scaffolds to generate peptidomimetics was first proposed by Fanner [1]. Carbohydrate moieties as scaffolds were first introduced by Hirschmann and Nicolaou [2].

Peptidic Inhibitors for Protein-Protein Interactions at Cell Surfaces

Interactions at cell surfaces are involved in a number of regulatory functions in living systems and therefore represent interesting drug targets such as the development of cyclic peptides and peptidomimetics of the RGD sequence [1]. Here we present two further examples diminishing a protein sequence into cyclic peptides with improved affinity, selectivity and enhanced proteolytic stability.