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    • 2. 发明授权
    • Therapeutic delivery using compounds self-assembled into high axial ratio microstructures
    • 使用化合物自组装成高轴比微结构的治疗输送
    • US06180114B2
    • 2001-01-30
    • US09219057
    • 1998-12-22
    • Paul YagerMichael H. GelbAnatoly N. LukyanovAlex S. GoldsteinMary L. Disis
    • Paul YagerMichael H. GelbAnatoly N. LukyanovAlex S. GoldsteinMary L. Disis
    • A61K900
    • A61K48/00A61K9/1274A61K47/6919
    • Therapeutic complexes comprising plural therapeutic compounds self assembled into high axial ratio microstructures are described. The therapeutic complexes satisfy the formula HARM-Th, wherein HARM is a high axial ratio forming material and Th is a therapeutic coupled to or associated with the HARM. The therapeutic complexes also can satisfy the formula HARM-S-Th, wherein S is a spacer. Release of the therapeutic by the complex generally follows either 0-order kinetics or psuedo-first order kinetics. A method for delivering therapeutics to oransims, particularly humans, also is described. The method comprises administering an effective amount of (1) a ligand, such as a therapeutic, self-assembled into a HAR microstructure, or (2) a ligand, such as a therapeutic, coupled to or associated with a material capable of thereafter self-assembling into a high axial ratio microstructure, to the mammal. Nucleic acids are an example of a ligand that can be administered effectively according to this method through noncovalent attachment to the HARM-forming materials.
    • 描述了包含自组装成高轴比微结构的多种治疗化合物的治疗复合物。 治疗复合物满足公式HARM-Th,其中HARM是高轴比形成材料,Th是与HARM偶联或与之相关的治疗剂。 治疗复合物还可以满足式HARM-S-Th,其中S是间隔物。 由复合物释放治疗剂通常遵循0级动力学或伪一级动力学。 还描述了将治疗剂递送到人类,特别是人类的方法。 该方法包括施用有效量的(1)配体,例如治疗性的,自组装的HAR微结构,或(2)配体,例如治疗剂,偶联或与其后自身的物质相关联 - 组装成高轴比比例的微结构,给哺乳动物。 核酸是可以根据该方法通过非共价连接到形成HARM的材料而有效施用的配体的实例。
    • 5. 发明授权
    • Rapid quantitative analysis of proteins or protein function in complex mixtures
    • 蛋白质或蛋白质功能在复杂混合物中的快速定量分析
    • US06670194B1
    • 2003-12-30
    • US09383062
    • 1999-08-25
    • Rudolf Hans AebersoldMichael H. GelbSteven P. GygiC. Ronald ScottFrantisek TurecekScott A. GerberBeate Rist
    • Rudolf Hans AebersoldMichael H. GelbSteven P. GygiC. Ronald ScottFrantisek TurecekScott A. GerberBeate Rist
    • C07C33116
    • G01N33/6848C12Q1/25G01N33/58G01N33/6803G01N33/6842Y10S530/812Y10T436/182Y10T436/24Y10T436/25Y10T436/25125Y10T436/25375
    • Analytical reagents and mass spectrometry-based methods using these reagents for the rapid, and quantitative analysis of proteins or protein function in mixtures of proteins. The methods employ affinity labeled protein reactive reagents having three portions: an affinity label (A) covalently linked to a protein reactive group (PRG) through a linker group (L). The linker may be differentially isotopically labeled, e.g., by substitution of one or more atoms in the linker with a stable isotope thereof. These reagents allow for the selective isolation of peptide fragments or the products of reaction with a given protein (e.g., products of enzymatic reaction) from complex mixtures. The isolated peptide fragments or reaction products are characteristic of the presence of a protein or the presence of a protein function in those mixtures. Isolated peptides or reaction products are characterized by mass spectrometric (MS) techniques. The reagents also provide for differential isotopic labeling of the isolated peptides or reaction products which facilitates quantitative determination by mass spectrometry of the relative amounts of proteins in different samples. The methods of this invention can be used for qualitative and quantitative analysis of global protein expression profiles in cells and tissues, to screen for and identify proteins whose expression level in cells, tissue or biological fluids is affected by a stimulus or by a change in condition or cell state of the cell, tissue or organism from which the sample originated.
    • 使用这些试剂的分析试剂和基于质谱的方法用于蛋白质混合物中蛋白质或蛋白质功能的快速和定量分析。 该方法采用具有三个部分的亲和标记的蛋白质反应试剂:通过连接基团(L)与蛋白质反应基团(PRG)共价连接的亲和标记(A)。 连接体可以是差异同位素标记的,例如用连接体中的一个或多个原子用其稳定同位素取代。 这些试剂允许从复杂混合物中选择性分离肽片段或与给定蛋白质(例如,酶反应产物)反应的产物。 分离的肽片段或反应产物是这些混合物中存在蛋白质或存在蛋白质功能的特征。 分离的肽或反应产物的特征在于质谱(MS)技术。 试剂还提供分离的肽或反应产物的差异同位素标记,其有助于通过质谱法定量测定不同样品中蛋白质的相对量。 本发明的方法可用于细胞和组织中全球蛋白质表达谱的定性和定量分析,筛选和鉴定细胞,组织或生物流体中的表达水平受刺激或病情变化影响的蛋白质 或来自样品的细胞,组织或生物体的细胞状态。
    • 9. 发明授权
    • Fluorine and chlorine statine or statone containing peptides and method
of use
    • 氟和氯他汀或含有肽的肽及其使用方法
    • US5066643A
    • 1991-11-19
    • US466803
    • 1990-01-18
    • Robert H. AbelesMichael H. Gelb
    • Robert H. AbelesMichael H. Gelb
    • C07C271/22C07K5/02
    • C07K5/0227C07C271/22
    • A peptide optionally in isosteric form wherein a methylene group in the backbone chain is disubstituted, one or both substituents being fluorine and/or chlorine, in free form or in pharmaceutically acceptable salt form, such as a compound of formula I ##STR1## wherein the substituents have various significances, or an isosteric form thereof,is useful as an enzyme inhibitor. In particular, as a renin inhibitor, it is useful in the prophylaxis or treatment of hypertension and congestive heart failure.It is prepared by a process comprising the step of coupling two corresponding peptide residues optionally in isosteric form, or precursors thereof, and if required appropriately converting any resultant compound in precursor form.
    • 任选处于等离子体形式的肽,其中主链中的亚甲基被二取代,游离形式或药学上可接受的盐形式的一种或两种取代基为氟和/或氯,例如式I化合物其中 取代基具有各种含义,或其等排形式可用作酶抑制剂。 特别是作为肾素抑制剂,可用于预防或治疗高血压和充血性心力衰竭。 其通过包括以下步骤的方法制备,所述方法将两个相应的肽残基任选地以等排形式或其前体偶联,并且如果需要,则适当地转化任何得到的前体形式的化合物。