公开(公告)号：WO2014070673A1

公开(公告)日：2014-05-08

申请号：PCT/US2013/067118

申请日：2013-10-28

Applicant: UNIVERSITY OF ROCHESTER

Inventor： FASAN, Rudi

IPC: C12N9/02 ,  C12N15/53 ,  A61K31/335

CPC classification number: C07D493/18 ,  C07D491/18 ,  C12N9/0042 ,  C12N9/0071 ,  C12P17/181 ,  C12Y106/02004 ,  C12Y114/00

Abstract: Derivatives of the antimalarial agent artemisinin, compositions comprising the derivatives, methods for preparing the derivatives, and their uses in pharmaceutical compositions intended for the treatment of parasitic infections are provided. Methods are provided for the production of artemisinin derivatives via functionalization of positions C7 and C6a, and optionally, in conjunction with modifications at positions C10 and C9, via chemoenzymatic methods. Recombinant cytochrome P450 polypeptides are also provided for use in the methods. The artemisinin derivatives can be used for the treatment of malaria and other parasitic infections, alone or in combination with other antiparasitic drugs.

Abstract translation: 提供了抗疟剂青蒿素的衍生物，包含衍生物的组合物，制备衍生物的方法及其用于治疗寄生虫感染的药物组合物中的用途。 提供了通过位置C7和C6a官能化生产青蒿素衍生物的方法，以及任选地通过化学酶法与C10和C9位置的修饰相结合。 还提供重组细胞色素P450多肽用于该方法。 青蒿素衍生物可用于单独或与其它抗寄生虫药物组合治疗疟疾和其他寄生虫感染。

公开(公告)号：WO2017099821A1

公开(公告)日：2017-06-15

申请号：PCT/US2016/000126

申请日：2016-12-08

Applicant: UNIVERSITY OF ROCHESTER

Inventor： GLEGHORN, Michael ,  MAQUAT, Lynne ,  FASAN, Rudi

IPC: C07K7/08 ,  C07K14/47 ,  A61K38/04

CPC classification number: C07K14/4747 ,  A61K38/00 ,  C07K7/08

Abstract: The invention provides compositions and methods for inhibiting protein- protein interactions with cap-binding protein 80 (CBP80). In one embodiment, the invention provides compositions comprising linear and macrocylic peptides. In one embodiment, the invention provides methods for treating cancer, heart disease, autoimmune disorders, obesity, diabetes, or chronic inflammation disorders associated with the PGC1 family of co-activators.

Abstract translation: 本发明提供了抑制蛋白质 - 蛋白质与帽结合蛋白80（CBP80）相互作用的组合物和方法。 在一个实施方案中，本发明提供了包含线性和大环肽的组合物。 在一个实施方案中，本发明提供了治疗癌症，心脏病，自身免疫性病症，肥胖症，糖尿病或与共同激活剂PGC1家族有关的慢性炎症疾病的方法。

公开(公告)号：WO2014197591A2

公开(公告)日：2014-12-11

申请号：PCT/US2014/040905

申请日：2014-06-04

Applicant: UNIVERSITY OF ROCHESTER

Inventor： FASAN, Rudi ,  JORDAN, Craig T. ,  KOLEV, Joshua N.

IPC: A61K31/5377 ,  C07D493/04

CPC classification number: C12P17/181 ,  C07D493/04 ,  C12N9/0042 ,  C12N9/0071 ,  C12Y106/02004 ,  C12Y114/14001

Abstract: Methods are provided for the generation of parthenolide derivatives functionalized at carbon atoms C9 and C14. Natural cytochrome P450 enzymes, and engineered variants of these enzymes, are used to carry out the hydroxylation of these sites in parthenolide. These P450-catalyzed C-H hydroxylation reactions are coupled to chemical interconversion of the enzymatically introduced hydroxyl group to install a broad range of functionalities at these otherwise unreactive sites of the molecule. The methods can also be used to produce bifunctionalized parthenolide derivatives, which in addition to modifications at the level of carbon atom C9 or C14, are also functionalized at the level of carbon atom C13.

Abstract translation: 提供了用于产生在碳原子C9和C14上官能化的小檗碱衍生物的方法。 天然细胞色素P450酶和这些酶的工程改造用于在小白菊内酯中进行这些位点的羟基化。 这些P450催化的C-H羟基化反应与酶促引入的羟基的化学相互作用相结合，以在分子的这些非反应性位点处安装宽范围的官能团。 该方法也可用于制备双官能化的单酚钠衍生物，除了在碳原子C 9或C 14的水平上进行修饰之外，还可以在碳原子C13的水平上进行官能化。

公开(公告)号：WO2016086015A1

公开(公告)日：2016-06-02

申请号：PCT/US2015/062478

申请日：2015-11-24

Applicant: UNIVERSITY OF ROCHESTER ,  FASAN, Rudi

Inventor： FASAN, Rudi

IPC: C12P17/18

CPC classification number: C12P13/001 ,  C07K14/805 ,  C12P5/002 ,  C12P9/00 ,  C12P11/00

Abstract: Methods are provided for carrying out carbene transfer transformations such as olefin cyclopropanation reactions, carbene heteroatom-H insertion reactions (heteroatom = N, S, Si), sigmatropic rearrangement reactions, and aldehyde olefination reactions with high efficiency and selectivity by using a novel class of myoglobin-based biocatalysts. These methods are useful for the synthesis of a variety of organic compounds which contain one or more new carbon-carbon or carbon-heteroatom (N, S, or Si) bond. The methods can be applied for conducting these transformations in vitro (i.e., using the biocatalyst in isolated form) and in vivo (i.e., using the biocatalyst in a whole cell system).

Abstract translation: 提供了用于通过使用新颖的类别的方法进行碳烯转移转化如烯烃环丙烷化反应，卡宾杂原子-H插入反应（杂原子= N，S，Si），信号重排反应和醛烯化反应，以高效率和选择性 基于肌红蛋白的生物催化剂。 这些方法可用于合成含有一个或多个新的碳 - 碳或碳 - 杂原子（N，S或Si）键的各种有机化合物。 该方法可用于体外进行这些转化（即，以分离形式使用生物催化剂）和体内（即，在整个细胞系统中使用生物催化剂）。

公开(公告)号：WO2012109586A2

公开(公告)日：2012-08-16

申请号：PCT/US2012/024723

申请日：2012-02-10

Applicant: UNIVERSITY OF ROCHESTER ,  FASAN, Rudi ,  ZHANG, Kaidong

Inventor： FASAN, Rudi ,  ZHANG, Kaidong

IPC: C12Q1/26 ,  C12N9/02 ,  C07C43/03

CPC classification number: C12Q1/26 ,  C12N15/102 ,  C12N15/1093 ,  C40B30/08 ,  G01N2333/90241 ,  G01N2333/90245

Abstract: Methods and systems for evaluating and predicting the reactivity of natural and engineered monooxygenase enzymes are provided. Methods are provided for acquiring a functional profile (fingerprint) of monooxygenases that encode information regarding the active site configuration of such monooxygenases. Methods are also provided for carrying out analysis of a monooxygenase fingerprint, to formulate predictions regarding the reactivity properties (e.g., substrate reactivity, chemo-, regio, and stereoselectivity properties) of the fingerprinted monooxygenases.

Abstract translation: 提供了用于评估和预测天然和工程化单加氧酶的反应性的方法和系统。 提供了用于获取编码关于这种单加氧酶的活性位点构型的信息的单加氧酶的功能谱（指纹图谱）的方法。 还提供了用于进行单加氧酶指纹分析的方法，以制定关于指纹图谱的单加氧酶的反应性（例如底物反应性，化学，区域和立体选择性）的预测。

公开(公告)号：WO2019040335A1

公开(公告)日：2019-02-28

申请号：PCT/US2018/046856

申请日：2018-08-17

Applicant: UNIVERSITY OF ROCHESTER

Inventor： FASAN, Rudi ,  GIOVANI, Simone ,  ALWASEEM, Hanan

IPC: C07D307/93 ,  A61K31/343 ,  A61P35/00

CPC classification number: C07D307/93 ,  A61P35/00

Abstract: The present invention relates to derivatives of the sesquiterpene lactone micheliolide, methods and compositions for their preparation, and methods for using the micheliolide derivatives in pharmaceutical compositions as anticancer and anti-inflammatory agents. The invention also relates to methods for producing micheliolide derivatives modified at positions C2 and C14. The invention also relates to methods for producing parthenolide derivatives modified at positions C2 and C14 in conjunction with modifications at position C13, via chemoenzymatic methods. The invention further relates to methods for using parthenolide derivatives for treating cancer and inflammatory diseases.

公开(公告)号：WO2017223207A1

公开(公告)日：2017-12-28

申请号：PCT/US2017/038559

申请日：2017-06-21

Applicant: UNIVERSITY OF ROCHESTER ,  FASAN, Rudi ,  OWENS, Andrew

Inventor： FASAN, Rudi ,  OWENS, Andrew

IPC: C07K7/50

Abstract: Cyclic peptide compounds are provided that can bind to one or more homologs of Hedghehog signaling proteins and block their interaction with the Patched receptor. These compounds are useful for suppressing Hedgehog-dependent stimulation of the Hedgehog pathway in cells and in living organisms. Methods for using the cyclic peptide compounds, and compositions comprising them, for treatment of cancers and other diseases which are characterized by aberrant Hedgehog-dependent activation of the Hedgehog pathway and/or which can benefit from chemical suppression of Hedgehog-dependent signaling are also disclosed.

Abstract translation: 提供了可结合一种或多种Hedghehog信号传导蛋白的同源物并阻断它们与Patched受体的相互作用的环肽化合物。 这些化合物可用于抑制Hedgehog通路在细胞和活体中的Hedgehog依赖性刺激。 还公开了使用环肽化合物和包含它们的组合物用于治疗以Hedgehog途径的异常Hedgehog依赖性激活为特征和/或可受益于化学抑制Hedgehog依赖性信号传导的癌症和其他疾病的方法

公开(公告)号：WO2015153761A2

公开(公告)日：2015-10-08

申请号：PCT/US2015/023883

申请日：2015-04-01

Applicant: UNIVERSITY OF ROCHESTER ,  FASAN, Rudi

Inventor： FASAN, Rudi

IPC: A61K38/12

CPC classification number: C07K7/54 ,  A61K38/00 ,  A61K38/12 ,  C07K7/06 ,  C07K7/08 ,  C07K14/001 ,  Y02A50/414

Abstract: Methods and compositions are provided for generating macrocyclic peptides constrained by side-chain-to-C-terminus non-peptidic tethers for use as functional and structural mimics of α-helical motifs, including in therapeutic applications. These methods can be used to produce libraries of conformationally constrained peptidomimetics to identify compounds with desired activity properties.

Abstract translation: 提供了用于产生被侧链至C端非肽链限制的大环肽的方法和组合物，用作α-螺旋基序的功能和结构模拟物，包括用于治疗应用。 这些方法可用于产生构象约束肽模拟物的文库，以鉴定具有期望活性性质的化合物。

公开(公告)号：WO2015100277A9

公开(公告)日：2015-07-02

申请号：PCT/US2014/072016

申请日：2014-12-23

Applicant: UNIVERSITY OF ROCHESTER ,  FASAN, Rudi

Inventor： FASAN, Rudi

IPC: C07K7/64

Abstract: Methods and compositions are provided for generating macrocyclic peptides from genetically encoded, ribosomally produced polypeptide precursors. Also provided are nucleic acid molecules, polypeptides, and methods for generating combinatorial libraries of macrocyclic peptides. These methods can be used to produce vast libraries of conformationally constrained peptide ligands as well as facilitate the functional screening of these libraries to identify compound(s) with desired activity properties.

公开(公告)号：WO2014039715A1

公开(公告)日：2014-03-13

申请号：PCT/US2013/058322

申请日：2013-09-05

Applicant: UNIVERSITY OF ROCHESTER

Inventor： FASAN, Rudi ,  FROST, John R.

IPC: C07K19/00 ,  G01N33/68

CPC classification number: C07K1/13 ,  A61K47/65 ,  A61K49/0039 ,  A61K49/0054 ,  C07C323/58 ,  C07C323/59 ,  C07C323/60 ,  C07D249/04 ,  C07D311/16 ,  C07D495/04 ,  C07K1/1072 ,  C07K14/35 ,  C07K2319/20 ,  C07K2319/21 ,  C07K2319/50 ,  C07K2319/60 ,  C07K2319/92 ,  C09B57/02 ,  C12N9/2442 ,  C12Y302/01014 ,  G01N33/582 ,  G01N33/6803

Abstract: Methods and compositions are provided for covalently linking a chemical species to a recombinant or synthetic polypeptide. The methods involve the reaction of a thioester-comprising polypeptide with a reagent comprising a reactive amino-thiol group connected to the chemical species which is to be covalently linked to the polypeptide, via a linker. Such chemical species can be a functional group, a label or tag molecule, a biological molecule, a ligand, or a solid support. Efficient and catalyst-free methods for C-terminal protein labeling are also provided. The methods expand current capabilities in the area of protein functionalization, providing useful and complementary tools for the isolation, detection, characterization, and analysis of proteins in a variety of in vitro and in vivo applications.

Abstract translation: 提供方法和组合物以共价连接化学物质与重组或合成的多肽。 该方法涉及含硫酯的多肽与包含通过连接体共价连接至多肽的化学物质连接的反应性氨基硫醇基团的试剂的反应。 这种化学物质可以是官能团，标记物或标签分子，生物分子，配体或固体支持物。 还提供了有效和无催化剂的C-末端蛋白标记方法。 该方法扩展了蛋白质功能化领域的当前能力，为各种体外和体内应用中蛋白质的分离，检测，表征和分析提供了有用和互补的工具。