公开(公告)号：US20150259368A1

公开(公告)日：2015-09-17

申请号：US14212173

申请日：2014-03-14

Applicant: Wisconsin Alumni Research Foundation

Inventor： Shannon S. Stahl ,  Joshua Coon ,  Alireza Rahimi ,  Arne Ulbrich

IPC: C07G1/00

CPC classification number: C07G1/00 ,  C07B41/06 ,  C08H6/00

Abstract: A method to cleave C—C and C—O bonds in β-O-4 linkages in lignin or lignin sub-units is described. The method includes oxidizing at least a portion of secondary benzylic alcohol groups in β-O-4 linkages in the lignin or lignin sub-unit to corresponding ketones and then leaving C—O or C—C bonds in the oxidized lignin or lignin sub-unit by reacting it with an organic carboxylic acid, a salt of an organic carboxylic acids, and/or an ester of an organic carboxylic acids. The method may utilize a metal or metal-containing reagent or proceed without the metal or metal-containing reagent.

Abstract translation: 描述了一种在木质素或木质素亚单元中裂解C-C和C-O键和b-o-4键的方法。 该方法包括将木质素或木质素亚单元中的b-O-4键中的至少一部分第二苄基醇氧化成相应的酮，然后将C-O或C-C键留在氧化的木质素或木质素亚中 - 通过使其与有机羧酸，有机羧酸的盐和/或有机羧酸的酯反应来进行。 该方法可以使用含金属或金属的试剂或不用金属或含金属的试剂进行。

公开(公告)号：US11525760B2

公开(公告)日：2022-12-13

申请号：US17365698

申请日：2021-07-01

Applicant: Wisconsin Alumni Research Foundation

Inventor： Joshua Coon ,  Michael Westphall

IPC: G01N1/42 ,  G01N1/36 ,  G01N15/14 ,  H01J49/16 ,  H01J37/28 ,  H01J37/26

Abstract: The present invention provides methods for controllably forming a layer of amorphous ice and other amorphous solids on a substrate, and also provides cryo-electron microscopy (cryo-EM) sample preparation methods and systems that utilize in vacuo formation of amorphous ice and other solids. Formation of the amorphous solid layer can be independent of the deposition of sample molecules to be analyzed using electron microscopy, and allows for the generation of a uniformly thick layer. Optionally, mass spectrometry instruments are used to generate and purify molecules deposited on the generated amorphous solid layer. The techniques and systems described herein can deliver near ideal cryo-EM sample preparation to greatly increase resolution, sensitivity, scope, and throughput of cryo-EM protein imaging, and therefore greatly impact the field of structural biology.

公开(公告)号：US12130217B2

公开(公告)日：2024-10-29

申请号：US17984934

申请日：2022-11-10

Applicant: Wisconsin Alumni Research Foundation

Inventor： Joshua Coon ,  Michael Westphall

IPC: G01N1/42 ,  G01N1/36 ,  G01N15/14 ,  H01J37/26 ,  H01J37/28 ,  H01J49/16

CPC classification number: G01N1/42 ,  G01N1/36 ,  G01N15/1468 ,  H01J37/26 ,  H01J37/28 ,  H01J49/164 ,  H01J49/165 ,  H01J2237/31745

Abstract: The present invention provides methods for controllably forming a layer of amorphous ice and other amorphous solids on a substrate, and also provides cryo-electron microscopy (cryo-EM) sample preparation methods and systems that utilize in vacuo formation of amorphous ice and other solids. Formation of the amorphous solid layer can be independent of the deposition of sample molecules to be analyzed using electron microscopy, and allows for the generation of a uniformly thick layer. Optionally, mass spectrometry instruments are used to generate and purify molecules deposited on the generated amorphous solid layer. The techniques and systems described herein can deliver near ideal cryo-EM sample preparation to greatly increase resolution, sensitivity, scope, and throughput of cryo-EM protein imaging, and therefore greatly impact the field of structural biology.

公开(公告)号：US12061204B2

公开(公告)日：2024-08-13

申请号：US17231977

申请日：2021-04-15

Applicant: Wisconsin Alumni Research Foundation

Inventor： Joshua Coon ,  Harald Marx

IPC: G01N33/68 ,  G16B30/00 ,  G16B30/20 ,  G16B40/00 ,  G16B40/10 ,  G16B40/30 ,  H01J49/00

CPC classification number: G01N33/6848 ,  G01N33/6824 ,  G01N33/6842 ,  G16B30/00 ,  G16B30/20 ,  G16B40/00 ,  G16B40/10 ,  G16B40/30 ,  H01J49/0036 ,  H01J49/004 ,  G01N2570/00

Abstract: In shotgun proteomics, generally only a fraction of peptides from a parent protein are actually detected. Because a large portion of the protein sequence is not detected, it is often impossible to determine whether the expressed protein is present in a modified, spliced, or truncated form. Provided herein are methods and systems for analyzing polypeptides which allow for the increase of the mean sequence coverage of a protein concomitant with bioinformatics analysis in order to distinguish putative proteoforms with improved amino acid resolution. Aspects of the invention include (1) a deep sequencing strategy to provide more protein sequence coverage than is typically achieved, and (2) a computational approach to view protein expression across its full length and identify regions of the protein that are potentially subject to such regulation. This technology has global utility in proteomics and will be of particular use for the analysis of biosimilar protein drug therapeutics.

公开(公告)号：US11092523B2

公开(公告)日：2021-08-17

申请号：US16626250

申请日：2018-07-06

Applicant: Wisconsin Alumni Research Foundation

Inventor： Joshua Coon ,  Michael Westphall

IPC: G01N1/42 ,  G01N1/36 ,  H01J37/26 ,  H01J37/28 ,  G01N15/14 ,  H01J49/16

Abstract: The present invention provides methods for controllably forming a layer of amorphous ice and other amorphous solids on a substrate, and also provides cryoelectron microscopy (cryo-EM) sample preparation methods and systems that utilize in vacuo formation of amorphous ice and other solids. Formation of the amorphous solid layer can be independent of the deposition of sample molecules to be analyzed using electron microscopy, and allows for the generation of a uniformly thick layer. Optionally, mass spectrometry instruments are used to generate and purify molecules deposited on the generated amorphous solid layer. The techniques and systems described herein can deliver near ideal cryo-EM sample preparation to greatly increase resolution, sensitivity, scope, and throughput of cryo-EM protein imaging, and therefore greatly impact the field of structural biology.

公开(公告)号：US09359391B2

公开(公告)日：2016-06-07

申请号：US14212173

申请日：2014-03-14

Applicant: Wisconsin Alumni Research Foundation

Inventor： Shannon S. Stahl ,  Joshua Coon ,  Alireza Rahimi ,  Arne Ulbrich

IPC: C08H8/00 ,  C07B41/06 ,  C08J3/00 ,  C07G1/00 ,  C08H7/00

CPC classification number: C07G1/00 ,  C07B41/06 ,  C08H6/00

Abstract: A method to cleave C—C and C—O bonds in β-O-4 linkages in lignin or lignin sub-units is described. The method includes oxidizing at least a portion of secondary benzylic alcohol groups in β-O-4 linkages in the lignin or lignin sub-unit to corresponding ketones and then leaving C—O or C—C bonds in the oxidized lignin or lignin sub-unit by reacting it with an organic carboxylic acid, a salt of an organic carboxylic acids, and/or an ester of an organic carboxylic acids. The method may utilize a metal or metal-containing reagent or proceed without the metal or metal-containing reagent.

Abstract translation: 描述了一种在木质素或木质素亚单元中裂解C-C和C-O键和b-o-4键的方法。 该方法包括将木质素或木质素亚单元中的b-O-4键中的至少一部分第二苄基醇氧化成相应的酮，然后将C-O或C-C键留在氧化的木质素或木质素亚中 - 通过使其与有机羧酸，有机羧酸的盐和/或有机羧酸的酯反应来进行。 该方法可以使用含金属或金属的试剂或不用金属或含金属的试剂进行。