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    AGENTS FOR BINDING TO ADVANCED GLYCOSYLATION ENDPRODUCTS, AND METHODS OF THEIR USE
    1.
    发明申请
    AGENTS FOR BINDING TO ADVANCED GLYCOSYLATION ENDPRODUCTS, AND METHODS OF THEIR USE 审中-公开
    用于结合高级糖苷化终产物的试剂及其使用方法

    公开(公告)号：WO1996031537A1

    公开(公告)日：1996-10-10

    申请号：PCT/US1996004755

    申请日：1996-04-05

    Applicant: THE PICOWER INSTITUTE FOR MEDICAL RESEARCH

    Inventor： THE PICOWER INSTITUTE FOR MEDICAL RESEARCH ,  LI, Yong, Ming ,  VLASSARA, Helen ,  CERAMI, Anthony

    IPC: C07K14/79

    CPC classification number: A61Q11/00 ,  A61K8/64 ,  A61K38/00 ,  B01L2400/0406 ,  C07K14/79 ,  C12N9/2462 ,  G01N33/68 ,  G01N33/6842 ,  G01N35/00069 ,  G01N2333/79 ,  G01N2333/924 ,  G01N2333/936 ,  Y10S530/811 ,  Y10S530/812 ,  Y10S530/815

    Abstract: The present invention is directed to diagnostic and therapeutic methods based on the unexpected discovery that certain antibacterial proteins, in particular lysozyme and lactoferrin, bind to advanced glycosylation endproducts (AGEs) with high affinity, and that this binding activity is substantially non-competitive with binding of bacterial carbohydrates to the antibacterial proteins. Accordingly, the invention relates to methods for treating diseases and disorders associated with increased levels of AGEs, by administering a molecule having a hydrophilic loop domain, which domain in lysozyme and lactoferrin is associated with AGE-binding activity, and compositions comprising such a domain. The invention further relates to methods and compositions for partitioning AGEs away from a sample. The invention is also directed to methods for determining a prognosis of AGE complications in a patient suffering from an AGE-associated disease or disorder by measuring the level of activity of antibacterial proteins, such as lysozyme and lactoferrin, in a biological sample from a subject. Decreased levels of antibacterial protein bacteriocidal activity may be indicative of increased levels of AGEs, and a prognostic indicator of increased susceptibility to bacterial infection. In a further aspect, the invention relates to detection of AGEs in a biological sample. In specific embodiments, AGEs inhibit the bacteriocidal activity of lysozyme and lactoferrin, and 17 or 18 amino acid hydrophilic loop peptides bracketed by cysteine (the first and last amino acids are cysteine that form a disulfide bond) bind to AGE-bovine serum albumin.

    Abstract translation: 本发明涉及基于意想不到的发现的某些抗菌蛋白质，特别是溶菌酶和乳铁蛋白与高亲和力的晚期糖基化终产物（AGE）结合的诊断和治疗方法，并且该结合活性与结合基本上非竞争性 的细菌碳水化合物对抗菌蛋白质。 因此，本发明涉及通过施用具有亲水环结构域的分子来治疗与增加的AGE水平相关的疾病和病症的方法，所述分子具有亲和性环结构域，溶菌酶和乳铁蛋白中的结构域与AGE结合活性相关，以及包含这种结构域的组合物。 本发明还涉及用于将AGEs分离离开样品的方法和组合物。 本发明还涉及通过测量来自受试者的生物样品中抗菌蛋白如溶菌酶和乳铁蛋白的活性水平来确定患有AGE相关疾病或病症的患者中AGE并发症的预后的方法。 抗菌蛋白杀菌活性水平的降低可能表明AGEs水平升高，以及细菌感染易感性增加的预后指标。 另一方面，本发明涉及检测生物样品中的AGEs。 在具体实施方案中，AGEs抑制溶菌酶和乳铁蛋白的杀细菌活性，并且由半胱氨酸（第一个和最后一个氨基酸是形成二硫键的半胱氨酸）包围的17或18个氨基酸亲水环肽与AGE-牛血清白蛋白结合。

    GUANYLHYDRAZONES FOR TREATING INFLAMMATORY CONDITIONS
    4.
    发明申请
    GUANYLHYDRAZONES FOR TREATING INFLAMMATORY CONDITIONS 审中-公开
    用于治疗炎症条件的GUANYLHYDRAZONES

    公开(公告)号：WO1995019767A1

    公开(公告)日：1995-07-27

    申请号：PCT/US1995000828

    申请日：1995-01-19

    Applicant: THE PICOWER INSTITUTE FOR MEDICAL RESEARCH

    Inventor： THE PICOWER INSTITUTE FOR MEDICAL RESEARCH ,  BIANCHI, Marina ,  CERAMI, Anthony ,  TRACEY, Kevin, J. ,  ULRICH, Peter

    IPC: A61K31/17

    CPC classification number: A61K31/621 ,  A61K31/00 ,  A61K31/155 ,  A61K31/167 ,  A61K31/17 ,  A61K31/175 ,  A61K31/195 ,  A61K31/4164 ,  A61K31/44 ,  A61K31/60 ,  C07C275/38 ,  C07C275/40 ,  C07C281/18 ,  Y10S514/825 ,  Y10S514/886 ,  Y10S514/903

    Abstract: This invention concerns new methods and compositions that are useful in preventing and ameliorating cachexia, the clinical syndrome of poor nutritional status and bodily wasting associated with cancer and other chronic diseases. More particularly, the invention relates to aromatic guanylhydrazone (more properly termed amidinohydrazone) compositions and their use to inhibit the uptake of arginine by macrophages and/or its conversion to urea. These compositions and methods are also useful in preventing the generation of nitric oxide (NO) by cells, and so to prevent NO-mediated inflammation and other responses in persons in need of same. In another embodiment, the compounds can be used to inhibit arginine uptake in arginine-dependent tumors and infections.

    Abstract translation: 本发明涉及可用于预防和改善恶病质的新方法和组合物，与癌症和其它慢性疾病相关的营养状况不佳的临床综合征以及身体的消耗。 更具体地说，本发明涉及芳香脒腙（更合适地称为脒基腙）组合物及其用于抑制巨噬细胞摄取精氨酸和/或转化成尿素的用途。 这些组合物和方法也可用于预防细胞产生一氧化氮（NO），并且因此可以防止需要相同的人的NO介导的炎症和其他反应。 在另一个实施方案中，所述化合物可用于抑制精氨酸依赖性肿瘤和感染中的精氨酸摄取。

    METHODS FOR MEASUREMENT AND TREATMENT PREDICATED ON THE PRESENCE OF ADVANCED GLYCOSYLATION ENDPRODUCTS IN TOBACCO AND ITS COMBUSTION BYPRODUCTS
    5.
    发明申请
    METHODS FOR MEASUREMENT AND TREATMENT PREDICATED ON THE PRESENCE OF ADVANCED GLYCOSYLATION ENDPRODUCTS IN TOBACCO AND ITS COMBUSTION BYPRODUCTS 审中-公开
    在烟草中先进的糖化终产物及其生产过程中预测的测量和处理方法

    公开(公告)号：WO1997023783A1

    公开(公告)日：1997-07-03

    申请号：PCT/US1996020526

    申请日：1996-12-23

    Applicant: THE PICOWER INSTITUTE FOR MEDICAL RESEARCH ,  ALTEON INC.

    Inventor： THE PICOWER INSTITUTE FOR MEDICAL RESEARCH ,  ALTEON INC. ,  CERAMI, Anthony ,  BUCALA, Richard, J. ,  VLASSARA, Helen ,  FOUNDS, Henry, W. ,  CERAMI, Clara, J.

    IPC: G01N33/68

    CPC classification number: G01N33/6842 ,  A24B15/36 ,  A24B15/365 ,  A24D3/14 ,  C07K14/415 ,  C07K16/16 ,  G01N33/54366 ,  G01N33/68

    Abstract: Methods are disclosed for measuring the accumulation of advanced glycosylation endproducts (AGEs), and for lowering the accumulation of advanced glycosylation endproducts, which are predicated on the discovery that such AGEs and their precedent glycotoxins are present in tobacco and its byproducts. More particularly the methods focus on the observation that individuals who smoke or otherwise use tobacco have increased levels of AGEs relative to non-smoking individuals. The present methods relate to the measurement of AGE levels in both individuals and in tobacco and its byproduct, smoke, and to the treatment of such individuals with agents capable of reacting with glycosylation products to either avert or diminish the accretion of AGEs in the body. Methods are also disclosed for the evaluation of the tobacco products to determine their storage status and organoleptic capacity and potential, for the treatment of the ambient atmosphere to lower AGE levels, and for the treatment of the tobacco products and combustion byproducts to lower AGE levels therein. For example, air or other samples may be taken and evaluated by a dosimeter or like device, to determine whether AGE levels exceed normal, after which measures could be implemented to remediate the ambient condition. Likewise, filters and similar devices for removing AGEs from tobacco smoke are disclosed. All such methods and corresponding materials are contemplated and included.

    Abstract translation: 公开了用于测量高级糖基化终产物（AGEs）的积累以及用于降低晚期糖基化终产物的积累的方法，这些发现是基于这样的发现，即AGE及其先例的糖类毒素存在于烟草及其副产物中。 更具体地说，这些方法着重于观察吸烟或以其他方式使用烟草的个体相对于非吸烟个体的AGEs水平的增加。 本方法涉及测量个体和烟草及其副产物，烟雾中的AGE水平，以及能够与糖基化产物反应的试剂对这些个体的治疗，以反转或减少AGEs在体内的积累。 还公开了评估烟草产品以确定其储存状态和感官能力和潜力的方法，用于处理环境大气以降低AGE水平，以及用于治疗烟草产品和燃烧副产物以降低AGE水平 。 例如，空气或其他样品可以通过剂量计或类似装置进行评估，以确定AGE水平是否超过正常，之后可以实施措施来修复环境条件。 同样地，公开了用于将AGE从烟草烟雾中除去的过滤器和类似装置。 所有这些方法和相应的材料都被考虑并包括在内。

    IMPROVED METHOD AND AGENTS FOR INHIBITING PROTEIN AGING
    6.
    发明申请
    IMPROVED METHOD AND AGENTS FOR INHIBITING PROTEIN AGING 审中-公开
    改进的抑制蛋白质老化的方法和试剂

    公开(公告)号：WO1997018223A1

    公开(公告)日：1997-05-22

    申请号：PCT/US1996018469

    申请日：1996-11-15

    Applicant: THE PICOWER INSTITUTE FOR MEDICAL RESEARCH

    Inventor： THE PICOWER INSTITUTE FOR MEDICAL RESEARCH ,  CERAMI, Anthony ,  AL-BED, Yousef ,  BUCALA, Richard, J. ,  ULRICH, Peter, C.

    IPC: C07H09/06

    CPC classification number: G01N33/6842 ,  A61K31/11 ,  C07H9/06 ,  C07H19/01 ,  G01N33/68

    Abstract: The present invention relates to compositions and methods for inhibiting the aging of amino-containing amino acid, peptides, proteins and biomolecules. Accordingly, a composition is disclosed which comprises an agent or compound capable of reacting with the glycosyl-amino moiety of the early glycosylation product (also known as the Amadori product or the Heyns product) formed by the reaction of glucose, or other reactive sugars, with an amino-containing peptide, protein or biomolecule, thus stabilizing this early glycosylation product, and preventing its further reaction to form open-chain, carbonyl-containing advanced glycosylation end products. Suitable agents may contain a reactive aldehyde group. A preferred agent is acetaldehyde. The method comprises contacting the target biomolecule with the composition. The compounds so obtained are represented by formulae (VI) and (VIII) wherein R is the residue of an amino-containing biomolecule such as a peptide and CH2R' is the residue of the reactive aldhehyde group. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.

    Abstract translation: 本发明涉及抑制含氨基酸，肽，蛋白质和生物分子的老化的组合物和方法。 因此，公开了一种组合物，其包含能够与由葡萄糖或其它反应性糖反应形成的早期糖基化产物（也称为Amadori产物或Heyns商品）的糖基 - 氨基部分反应的试剂或化合物， 含有氨基的肽，蛋白质或生物分子，从而稳定该早期糖基化产物，并防止其进一步反应形成开链的含羰基的高级糖基化终产物。 合适的试剂可以含有反应性醛基。 优选的试剂是乙醛。 该方法包括使目标生物分子与组合物接触。 如此获得的化合物由式（VI）和（VIII）表示，其中R是含氨基的生物分子的残基，例如肽，而CH2R'是反应性脱乙酰基的残基。 预想到本发明的工业和治疗应用，因为可以处理食物腐败和动物蛋白质老化。

    GLYCOSYLATION OF LIPIDS AND LIPID-CONTAINING PARTICLES, AND DIAGNOSTIC AND THERAPEUTIC METHODS AND MATERIALS DERIVED THEREFROM
    8.
    发明申请
    GLYCOSYLATION OF LIPIDS AND LIPID-CONTAINING PARTICLES, AND DIAGNOSTIC AND THERAPEUTIC METHODS AND MATERIALS DERIVED THEREFROM 审中-公开
    脂肪和含脂肪颗粒的糖化，以及诊断和治疗方法及其衍生的材料

    公开(公告)号：WO1994020083A1

    公开(公告)日：1994-09-15

    申请号：PCT/US1993010880

    申请日：1993-11-12

    Applicant: THE PICOWER INSTITUTE FOR MEDICAL RESEARCH

    Inventor： THE PICOWER INSTITUTE FOR MEDICAL RESEARCH ,  BUCALA, Richard, J. ,  VLASSARA, Helen ,  CERAMI, Anthony

    IPC: A61K31/155

    CPC classification number: G01N33/533 ,  A61K31/00 ,  A61K31/155 ,  A61K31/195 ,  A61K31/415 ,  A61K31/70 ,  A61K38/1709 ,  G01N33/6893 ,  G01N33/92 ,  G01N2800/042 ,  G01N2800/044 ,  G01N2800/323

    Abstract: The in vivo oxidation of lipids and lipid-containing molecules has been discovered to be initiated by the concurrent reaction of such lipid materials with reducing sugars such as glucose, advanced glycosylation endproducts such as AGE-peptides, or a compound which forms advanced glycosylation endproducts, to form materials or particles known as AGE-lipids. AGE-lipids have been implicated in the aging process, the abnormal formation of lipofuscin and invarious disease states such as diabetes and atherosclerosis. Diagnostic methods are contemplated, extending in utility from the detection of the onset and course of conditions in which variations in lipid oxidation, AGE-lipid levels, LDL levels, apolipoprotein levels, apolipoprotein receptor binding the like, may be measured, to drug discovery assays. Corresponding methods of treatment and pharmaceutical compositions are disclosed that are based on an active ingredient or ingredients that demonstrate the ability to modulate the levels of all the foregoing markers of lipid oxidation.

    Abstract translation: 已经发现脂质和含脂质分子的体内氧化是通过这种脂质物质与还原糖如葡萄糖，高级糖基化终产物例如AGE-肽或形成晚期糖基化终产物的化合物的同时反应引发的， 形成称为AGE-脂质的材料或颗粒。 AGE-脂质已经涉及老化过程，脂褐素异常形成和诸如糖尿病和动脉粥样硬化等疾病状态。 考虑到诊断方法，从检测可以测量脂质氧化，AGE-脂质水平，LDL水平，载脂蛋白水平，结合载脂蛋白受体等的药物发现测定 。 公开了相应的治疗方法和药物组合物，其基于表现出调节所有前述脂质氧化标记物水平的能力的活性成分或成分。

    TREATMENT OF HIV-INFECTION BY INTERFERING WITH HOST CELL CYCLOPHILIN RECEPTOR ACTIVITY
    9.
    发明申请
    TREATMENT OF HIV-INFECTION BY INTERFERING WITH HOST CELL CYCLOPHILIN RECEPTOR ACTIVITY 审中-公开
    通过干扰宿主细胞环磷酰胺受体活性来治疗艾滋病毒感染

    公开(公告)号：WO1997033604A1

    公开(公告)日：1997-09-18

    申请号：PCT/US1997003819

    申请日：1997-03-12

    Applicant: PICOWER INSTITUTE FOR MEDICAL RESEARCH

    Inventor： PICOWER INSTITUTE FOR MEDICAL RESEARCH ,  BUKRINSKY, Michael ,  SHERRY, Barbara, A. ,  ULRICH, Peter, C. ,  CERAMI, Anthony

    IPC: A61K38/13

    CPC classification number: C07K16/40 ,  A61K38/13 ,  A61K38/52

    Abstract: There is disclosed pharmaceutical compositions for the treatment of HIV-infection using cyclophilin A and its corresponding human cellular binding partner as a target for intervention. There is further disclosed a method of using cyclophilins, anti-cyclophilin antibodies, and pegylated cyclosporin A as a treatment for HIV-infection. The present invention further provides screening assays for the identification of compounds which inhibit the interaction of cyclophilin and its cellular receptor.

    Abstract translation: 公开了使用亲环蛋白A及其相应的人细胞结合配偶体作为干预靶标来治疗HIV感染的药物组合物。 还公开了使用亲环蛋白，抗亲环蛋白抗体和聚乙二醇化环孢菌素A作为HIV感染治疗的方法。 本发明进一步提供了用于鉴定抑制亲环蛋白及其细胞受体的相互作用的化合物的筛选试验。

    SCREENING ASSAY FOR THE IDENTIFICATION OF INHIBITORS OF MACROPHAGE MIGRATION INHIBITORY FACTOR
    10.
    发明申请
    SCREENING ASSAY FOR THE IDENTIFICATION OF INHIBITORS OF MACROPHAGE MIGRATION INHIBITORY FACTOR 审中-公开
    用于识别大量移动抑制因子抑制剂的筛选测定

    公开(公告)号：WO1997029635A1

    公开(公告)日：1997-08-21

    申请号：PCT/US1997002448

    申请日：1997-02-14

    Applicant: PICOWER INSTITUTE FOR MEDICAL RESEARCH

    Inventor： PICOWER INSTITUTE FOR MEDICAL RESEARCH ,  BUCALA, Richard ,  ULRICH, Peter, C. ,  XHANG, Xini ,  CERAMI, Anthony ,  BENDRAT, Klaus

    IPC: A01N43/34

    CPC classification number: A61K31/404 ,  A61K38/00 ,  C07K14/52

    Abstract: There is disclosed assays to identify compounds that inhibit an enzymatic activity of MIF (macrophage migration inhibitory factor). The enzyme activity catalyzes a tautomerization of MIF-substrates, such as D-dopachrome to DHICA. In general, the assay is conducted in vitro by adding, mixing or combining MIF polypeptide and a suitable substrate in the presence or absence of a test compound, and measuring the tautomerization of the substrate. The test compounds that inhibit tautomerization in the assay are identified as MIF inhibitors.

    Abstract translation: 公开了鉴定抑制MIF的酶活性（巨噬细胞迁移抑制因子）的化合物的测定法。 酶活性催化MIF-底物的互变异构，例如D-多巴色素到DHICA。 通常，通过在存在或不存在测试化合物的情况下通过加入，混合或组合MIF多肽和合适的底物并测量底物的互变异构体进行测定。 在测定中抑制互变异构化的测试化合物被鉴定为MIF抑制剂。

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