Methods for screening compound libraries

a compound library and library technology, applied in chemical libraries, combinational chemistry, component separation, etc., can solve the problems of inability to identify compounds having the desired biological activity, need to keep track, and inability to screen each compound individually, so as to reduce the screening time for each library, shorten the break through time, and achieve the effect of weak affinity for the target receptor

a compound library and library technology, applied in chemical libraries, combinational chemistry, component separation, etc., can solve the problems of inability to identify compounds having the desired biological activity, need to keep track, and inability to screen each compound individually, so as to reduce the screening time for each library, shorten the break through time, and achieve the effect of weak affinity for the target receptor

US20040053336A1Inactive Publication Date: 2004-03-18HINDSGAUL OLE +1
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  • Methods for screening compound libraries
  • Methods for screening compound libraries
  • Methods for screening compound libraries

Examples

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example 1

Screening of an Oligosaccharide Library Using FC-MS

[0210] In this example, a compound library containing a mixture of six oligosaccharides was screened using frontal chromatography in combination with an electrospray mass spectrometer to determine the relative affinity of the oligosaccharides for a monoclonal antibody that recognizes the 3,6-dideoxy-D-galactose (abequose) epitope in Salmonella paratyphi B O-antigens.

[0211] The compound library consisted of the following six oligosaccharides: .alpha.GalNAc(1.fwdarw.3).beta.Gal-OGr (compound 1); .alpha.Gal(1.fwdarw.3)[.alpha.Fuc(1.fwdarw.2)].beta.Gal-OGr (compound 2); .alpha.Man(1.fwdarw.3)[.alpha.Man(1.fwdarw.6)].beta.Man-OGr (compound 3); .alpha.Abe(1.fwdarw.3).alpha.Tal-OCH.sub.3 (compound 4); .alpha.Gal(1.fwdarw.2)[.alpha.Abe(1.fwdarw.3)].alpha.Man-OCH.sub.3 (compound 5); and .alpha.Glc(1.fwdarw.4).beta.Glc(1.fwdarw.4).alpha.Gal(1-.fwdarw.2)-[.alpha.Abe(1.fwdarw.3)].alpha.Man(1.fwdarw.3).alpha.Glc(1.fwda-rw.4).beta.Glc-OCH.sub.3 (...

example 2

Screening of an Oligosaccharide Library Using FC-MS and an Indicator Compound

[0223] In this example, the use of an indicator compound to screen a compound library is demonstrated. The antibody used in this example was the same as that used in Example 1, i.e., a monoclonal antibody that recognizes the 3,6-dideoxy-D-galactose (abequose) epitope in Salmonella paratyphi B O-antigens. The column was also essentially the same as the column in Example 1 and it was prepared and operated as described therein.

[0224] In this experiment, three solutions were prepared. Solution A contained the following four oligosaccharide in 2 mM NH.sub.4OAc: .alpha.GalNAc(1.fwdarw.3).beta.Gal-OGr (compound 1); .alpha.Gal(1.fwdarw.3)[.alpha.Fuc(1.fwdarw.2)].beta.Gal-OGr (compound 2);

[0225] .alpha.Man(1.fwdarw.3)[(.alpha.Man(1.fwdarw.6)].beta.Man-OGr (compound 3); .alpha.Abe(1.fwdarw.3).alpha.Tal-OCH.sub.3 (compound 4), wherein Gr=O(CH.sub.2).sub.8CO.sub.2CH.sub.3. Solution B contained

[0226] .alpha.Gal(1.fwdarw...

example 3

Screening of an Oligosaccharide Library Using FC-MS

[0230] In this example, a compound library containing a mixture of four oligosaccharides was screened using frontal chromatography in combination with an electrospray mass spectrometer to determine the relative affinity of the oligosaccharides for cholera toxin B subunit.

[0231] The compound library consisted of the following four oligosaccharides: .alpha.GalNAc(1.fwdarw.3).beta.Gal-OGr (compound 1); .alpha.Gal(1.fwdarw.3)[.alpha.Fuc(1.fwdarw.2)].beta.Gal-OGr (compound 2); .alpha.Man(1.fwdarw.3)[.alpha.Man(1.fwdarw.6)].beta.Man-OGr (compound 3); and GM.sub.1 oligosaccharide (compound 7, wherein Gr=O(CH.sub.2).sub.8CO.-sub.2CH.sub.3. Compound 7, which is the natural ligand for cholera toxin B subunit, was obtained using the procedures described in A. Schon et al., "Thermodynamics of Intersubunit Interactions in Cholera Toxin upon Binding to the Oligosaccharide Portion of Its Cell Surface Receptor, Ganglioside G.sub.M1" Biochem. 1989, ...

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Abstract

Disclosed are methods for screening compound libraries using frontal chromatography in combination with mass spectrometry to identify and rank those members of the library that bind to a target receptor. Methods are also disclosed which permit a compound library to be rapidly screened to determine if any member of the library has an affinity for the target receptor as measured by a pre-selected indicator compound.

Description

[0001] This application is a continuation-in-part of U.S. Ser. No. ______, filed Dec. 28, 1998 (Attorney Docket No. 026579-248); which application is a continuation of U.S. Ser. No. 09 / 070,131, filed Apr. 29, 1998, now abandoned; which application claims the benefit of U.S. Provisional Application No. 60 / 079,622, filed Mar. 27, 1998. Each of these applications are incorporated herein by reference in their entirety.[0002] 1. Field of the Invention[0003] This invention relates to methods for screening compound libraries, such as compound libraries generated using combinatorial chemistry techniques. The methods of this invention employ frontal chromatography in combination with mass spectrometry to screen a library of compounds to identify and rank those members of the library that bind to a target receptor. The methods of this invention also permit a compound library to be rapidly screened to determine if one or more members of the library have an affinity for a target receptor as mea...

Claims

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Application Information

Patent Timeline
18 Mar 2004
Publication
US20040053336A1
IPC
C40B30/08; C40B40/12; C40B40/18; G01N30/46; G01N30/62; G01N30/72; G01N33/538; G01N33/543; G01N33/68; H01J49/04
CPC
B01J2219/00585; Y10T436/24; B01J2219/00707; B01J2219/00731; B01J2219/00738; B01J2219/00745; B01J2219/00747; C40B30/08
Inventors
HINDSGAUL, OLE; SCHRIEMER, DAVID C.