1541175-37-4

Upstream product

• 16257-79-7 methyl (2S,4S)-4-hydroxy-1-(phenylsulfonyl)pyrrolidine-2-carboxylate 
• 873847-24-6 methyl (2S,4R)-4-azido-1-(phenylsulfonyl)pyrrolidine-2-carboxylate 
• 1541175-32-9 (2S,4R)-4-azido-1-(phenylsulfonyl)pyrrolidine-2-carboxylic acid 
• 1541175-33-0 4-((2S)-2-((2S,4R)-4-azido-1-(phenylsulfonyl)pyrrolidine-2-carboxamido)-3-methoxy-3-oxopropyl)phenyl pyrrolidine-1-carboxylate 
• 16257-76-4 1-(benzenesulphonyl)-4-hydroxypyrrolidine-2-carboxylic acid 
• 1192-63-8 1-pyrrolidinecarbonyl chloride 
• 13512-31-7 N-(benzyloxycarbonyl)-L-tyrosine methyl ester 
• 873847-23-5 C₁₃H₁₇NO₇S₂ 
• 1541175-25-0 (S)-4-(2-(((benzyloxy)carbonyl)amino)-3-methoxy-3-oxopropyl)phenyl pyrrolidine-1-carboxylate 
• 1541175-26-1 4-((2S)-2-((2S,4S)-4-hydroxy-1-(phenylsulfonyl)pyrrolidine-2-carboxamido)-3-methoxy-3-oxopropyl)phenyl pyrrolidine-1-carboxylate 

Downstream Products

• 1541175-39-6 R-BC₁₅₄ 

Relevant academic research and scientific papers

DISLODGEMENT AND RELEASE OF HSC USING ALPHA 9 INTEGRIN ANTAGONIST AND CXCR4 ANTAGONIST

Haematopoietic stem cell mobilization is a process whereby haematopoietic stem cells are stimulated out of the bone marrow space. Before HSC can mobilize, they must be dislodged and released from the BM stem cell niche in which they reside and are retained by adhesive interactions. Accordingly, in an aspect of the present invention there is provided a method for enhancing dislodgement of HSC and their precursors and progenitors thereof from a BM stem cell binding ligand in vivo or ex vivo, said method comprising administering in vivo or ex vivo an effective amount of an antagonist of an α9 integrin or an active portion thereof and a CXCR4 antagonist or an active portion thereof to the BM stem cell niche. Once mobilized to the peripheral blood (PB) the HSC may be collected for transplant. Methods which enhance mobilization of the HSC can also improve treatments of haematological disorders.

Design, synthesis and binding properties of a fluorescent α9β1/α4β1 integrin antagonist and its application as an in vivo probe for bone marrow haemopoietic stem cells

The α9β1 and α4β 1 integrin subtypes are expressed on bone marrow haemopoietic stem cells and have important roles in stem cell regulation and trafficking. Although the roles of α4β1 integrin have been thoroughly investigated with respect to HSC function, the role of α9β1 integrin remains poorly characterised. Small molecule fluorescent probes are useful tools for monitoring biological processes in vivo, to determine cell-associated protein localisation and activation, and to elucidate the mechanism of small molecule mediated protein interactions. Herein, we report the design, synthesis and integrin-dependent cell binding properties of a new fluorescent α9β 1 integrin antagonist (R-BC154), which was based on a series of N-phenylsulfonyl proline dipeptides and assembled using the Cu(i)-catalyzed azide alkyne cycloaddition (CuAAC) reaction. Using transfected human glioblastoma LN18 cells, we show that R-BC154 exhibits high nanomolar binding affinities to α9β1 integrin with potent cross-reactivity against α4β1 integrin under physiological mimicking conditions. On-rate and off-rate measurements revealed distinct differences in the binding kinetics between α9β 1 and α4β1 integrins, which showed faster binding to α4β1 integrin relative to α9β1, but more prolonged binding to the latter. Finally, we show that R-BC154 was capable of binding rare populations of bone marrow haemopoietic stem and progenitor cells when administered to mice. Thus, R-BC154 represents a useful multi-purpose fluorescent integrin probe that can be used for (1) screening small molecule inhibitors of α9β 1 and α4β1 integrins; (2) investigating the biochemical properties of α9β 1 and α4β1 integrin binding and (3) investigating integrin expression and activation on defined cell phenotypes in vivo.