公开(公告)号：US20160280632A1

公开(公告)日：2016-09-29

申请号：US15174306

申请日：2016-06-06

Applicant: WISCONSIN ALUMNI RESEARCH FOUNDATION

Inventor： Samuel Helmer Gellman ,  Li Guo ,  Michael Giuliano

IPC: C07C205/44 ,  C07C205/55 ,  C07C201/12

CPC classification number: C07C205/44 ,  C07C201/12 ,  C07C205/55 ,  C07C233/48 ,  C07C237/24 ,  C07C269/00 ,  C07C271/24 ,  C07C271/66 ,  C07C2601/08 ,  C07C2601/14 ,  C07D211/56 ,  C07D211/60 ,  C07K5/0205 ,  C07K5/06078 ,  C07K5/1016 ,  C07K7/06

Abstract: The invention provides compounds and methods, for example, to carry out organocatalytic Michael additions of aldehydes to cyclically constrained nitroethylene compounds catalyzed by a proline derivative to provide cyclically constrained α-substituted-γ-nitro-aldehydes. The reaction can be rendered enantioselective when a chiral pyrrolidine catalyst is used, allowing for Michael adducts in nearly optically pure form (e.g., 96 to >99% e.e.).The Michael adducts can bear a single substituent or dual substituents adjacent to the carbonyl. The Michael adducts can be efficiently converted to cyclically constrained protected γ-amino acid residues, which are essential for systematic conformational studies of γ-peptide foldamers. New methods are also provided to prepare other γ-amino acids and peptides. These new building blocks can be used to prepare foldamers, such as α/γ-peptide foldamers, that adopt specific helical conformations in solution and in the solid state.

Abstract translation: 迈克尔加合物可以承受单个取代基或与羰基相邻的双取代基。 迈克尔加合物可以有效地转化为循环受限的受保护的γ-氨基酸残基，这对于γ-肽折叠物的系统构象研究至关重要。 还提供了新的方法来制备其它γ-氨基酸和肽。 这些新的构建块可用于制备在溶液中和固体状态下采用特定螺旋构象的折叠物，例如α/γ-肽折叠物。

公开(公告)号：US09255122B2

公开(公告)日：2016-02-09

申请号：US14556544

申请日：2014-12-01

Applicant: Wisconsin Alumni Research Foundation

Inventor： Samuel Helmer Gellman ,  Pil Seok Chae

IPC: C07C257/00 ,  C07C263/00 ,  C07K1/14 ,  C07J41/00

CPC classification number: C07K1/14 ,  C07J41/00 ,  C07J41/0061 ,  C07K1/145

Abstract: Disclosed are compounds and methods for manipulating proteins in general and membrane proteins in particular. The compounds can be prepared from cholic acid, deoxycholic acid, lithocholic acid, or derivatives thereof. The compounds typically possess critical micelle concentrations lower than those of known detergents such as CHAPS and CHAPSO. Accordingly, lower amounts of the compounds are required for effective solubilization of membrane proteins. The compounds can be used aid the solubilization, isolation, purification, stabilization, crystallization, and/or structural determination of membrane proteins.

Abstract translation: 公开的是一般操作蛋白质和特别是膜蛋白质的化合物和方法。 该化合物可以由胆酸，脱氧胆酸，石胆酸或其衍生物制备。 这些化合物通常具有低于已知洗涤剂如CHAPS和CHAPSO的临界胶束浓度。 因此，为了有效溶解膜蛋白质，需要较低量的化合物。 这些化合物可用于帮助膜蛋白的溶解，分离，纯化，稳定化，结晶和/或结构测定。

公开(公告)号：US08815263B2

公开(公告)日：2014-08-26

申请号：US13669198

申请日：2012-11-05

Applicant: Wisconsin Alumni Research Foundation

Inventor： Pil Seok Chae ,  Samuel Helmer Gellman

IPC: A61K9/00 ,  C07K1/00 ,  A23J1/00 ,  C07J41/00

CPC classification number: C07J43/003 ,  A61B34/30 ,  A61B90/361 ,  A61B2034/301 ,  A61B2090/3782 ,  A61K9/107 ,  A61K47/26 ,  A61K47/28 ,  C07J9/00 ,  C07J31/006 ,  C07J41/0061 ,  C07J51/00 ,  C07K1/145

Abstract: The invention provides tandem facial amphiphiles for biochemical manipulations and characterization of membrane proteins, such as intrinsic membrane proteins. Members of this new family display favorable behavior with several membrane proteins. These amphiphiles can form relatively small micelles, and small changes in amphiphile chemical structures can result in large changes in their physical properties. The tandem facial amphiphiles can be used to aid the solubilization, isolation, purification, stabilization, crystallization, and/or structural determination of membrane proteins.

Abstract translation: 本发明提供用于生物化学操作和膜蛋白（例如内在膜蛋白）表征的串联面部两亲物。 这个新家庭的成员显示有几种膜蛋白的有利行为。 这些两亲物可以形成相对较小的胶束，并且两亲化学结构的小变化可导致其物理性质的大的变化。 串联面部两亲物可用于帮助膜蛋白的溶解，分离，纯化，稳定化，结晶和/或结构测定。