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公开(公告)号：US06914048B2
公开(公告)日：2005-07-05
申请号：US10246441
申请日：2002-09-18
CPC分类号： C07K7/08 , A61K47/645 , C07K7/06
摘要： Disclosed are β-peptides and β-peptide conjugates that are capable of diffusing or otherwise being transported across the cell membranes of living cells. The β-peptides contain at least six β-amino acid residues, at leastsix of which are preferably β3-homoarginine residues. It has been found that when pharmacologically-active agents are conjugated to these types of β-peptides, the resulting conjugates (also disclosed herein) are also capable of diffusing or otherwise being transported across the cell membranes of living cells, including mammalian cells.
摘要翻译： 公开了能够扩散或以其它方式被传输通过活细胞细胞膜的β-肽和β-肽缀合物。 β-肽含有至少六个β-氨基酸残基，其中至少有七个是优质β-OH-精氨酸残基。 已经发现，当药理活性剂与这些类型的β-肽缀合时，所得到的缀合物（本文也公开）也能够扩散或以其它方式被传输穿过包括哺乳动物细胞的活细胞的细胞膜。
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公开(公告)号：US09758569B2
公开(公告)日：2017-09-12
申请号：US11807270
申请日：2007-05-25
CPC分类号： C07K14/78 , C07K5/0821 , C07K14/001
摘要： Novel collagen mimics are disclosed with a tripeptide unit having the formula (Xaa-Yaa-Gly)n, where one of the positions Xaa or Yaa is a bulky, non-electron withdrawing proline derivative. By substituting a proline derivative at either the Xaa or Yaa position in the native collagen helix, the stability of the helix is increased due solely to steric effects relative to prior known collagen-related triple helices. Methods are also disclosed for making the novel collagen mimics.
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公开(公告)号：US08293872B2
公开(公告)日：2012-10-23
申请号：US13243373
申请日：2011-09-23
IPC分类号： C07K1/00
摘要： This invention relates to cytotoxic variants of human ribonuclease 1 (RNase 1) identified through analysis of the interaction between RNase 1 and the human ribonuclease inhibitor (hRI) as defined by the three dimensional (3-D) atomic structure of the RNase1 hRI complex. Also disclosed is the 3-D structure of the hRI•RNase 1 complex and methods for designing the RNase 1 variants.
摘要翻译： 本发明涉及通过分析由RNase1 hRI复合物的三维（3-D）原子结构定义的核糖核酸酶1和人核糖核酸酶抑制剂（hRI）之间的相互作用而鉴定的人核糖核酸酶1（核糖核酸酶1）的细胞毒性变体。 还公开了hRI·RNase 1复合物的3-D结构和用于设计RNA酶1变体的方法。
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公开(公告)号：US07932239B2
公开(公告)日：2011-04-26
申请号：US11412353
申请日：2006-04-27
申请人： Ronald T. Raines , Leonard A. Levin
发明人： Ronald T. Raines , Leonard A. Levin
摘要： Methods and compositions involving a class of boron-protected phenylphosphine agents having increased cell permeability and having improved chemical stability for treating or for preventing neuronal cell death-related diseases or conditions in a human or a non-human animal.
摘要翻译： 涉及一类具有增强的细胞通透性并具有改善的化学稳定性的硼保护的苯基膦试剂的方法和组合物，用于治疗或预防人类或非人动物中的神经元细胞死亡相关疾病或病症。
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5.发明申请STABILIZATION OF THE COLLAGEN TRIPLE HELIX BY O-METHYLATION OF HYDROXYPROLINE RESIDUES 有权通过羟基丙烯酸残基的O-甲基化对胶原三肽螺旋体的稳定化公开(公告)号：US20090264626A1
公开(公告)日：2009-10-22
申请号：US12367374
申请日：2009-02-06
申请人： Ronald T. Raines , Frank W. Kotch
发明人： Ronald T. Raines , Frank W. Kotch
IPC分类号： C07K14/78
CPC分类号： C07K14/78
摘要： This invention relates to a collagen polypeptide comprising a tripeptide motif having the formula (ProYaaGly)n, where Yaa is an O-methylated amino acid residue and “n” is the number of motif repeats. Preferred O-methylated amino acid residues at the Yaa position include (2S,4R)-4-methoxyproline. Other suitable amino acid residues at that position include O-mono or O-di-halogenated methylproline. Also, disclosed is a method of making a synthetic or a semi-synthetic collagen polypeptide molecule having increased stability relative to natural collagen. The strengthened collagen molecules are suitable for use in biomaterials for the medical field or in leather-related products prepared by the tanning industry.
摘要翻译： 本发明涉及包含具有式（ProYaaGly）n的三肽基序的胶原多肽，其中Yaa是O-甲基化氨基酸残基，“n”是基序重复的数目。 在Yaa位置优选的O-甲基化氨基酸残基包括（2S，4R）-4-甲氧基脯氨酸。 该位置上的其它合适的氨基酸残基包括O-单或O-二卤代甲基脯氨酸。 此外，还公开了制备相对于天然胶原蛋白具有增加的稳定性的合成或半合成胶原多肽分子的方法。 强化的胶原分子适用于医疗领域的生物材料或由鞣革行业制备的皮革相关产品。
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公开(公告)号：US07534902B2
公开(公告)日：2009-05-19
申请号：US10988979
申请日：2004-11-15
IPC分类号： C07D311/82 , C07D311/78 , C07D311/88
CPC分类号： C12Q1/34 , C07D493/10 , C09B11/24 , C09B19/00 , G01N33/581 , G01N33/582 , G01N2333/916 , G01N2333/924
摘要： Latent fluorescent compounds, comprising a fluorescent molecule with one or more blocking groups attached and optionally one or more urea-containing groups are provided. The urea-containing group can be used to further attach one or more molecules of interest, such as proteins, peptides or nucleic acids. The blocking group(s) is released from the latent fluorescent compound by reaction with a trigger, forming the fluorescent molecule which can be detected. Also provided herein are methods of using latent fluorescent compounds to detect triggers.
摘要翻译： 提供了包含具有一个或多个连接基团和任选的一个或多个含脲基团的荧光分子的潜在荧光化合物。 含尿素基团可用于进一步连接一种或多种感兴趣的分子，例如蛋白质，肽或核酸。 通过与触发剂反应，阻断基团从潜在荧光化合物释放，形成可被检测的荧光分子。 本文还提供了使用潜伏荧光化合物来检测触发剂的方法。
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公开(公告)号：US20080286345A1
公开(公告)日：2008-11-20
申请号：US12017953
申请日：2008-01-22
CPC分类号： A61K9/7007 , A61K47/645
摘要： A composition for delivery of a molecule into a cell is provided. The composition includes a protein transduction domain that is conjugated to the molecule which is incorporated into a multilayered film. Preferably, the protein transduction domain is a cationic protein transduction domain. More preferably, the cationic protein transduction domain is nonaarginine, and the multilayered film includes polyelectrolyte multilayers. When the composition is presented to a cell, the multilayered film dissolves or erodes in physiological media, and the molecule is delivered into the cell.
摘要翻译： 提供了将分子递送到细胞中的组合物。 该组合物包括与分子结合的蛋白转导结构域，其结合到多层膜中。 优选地，蛋白质转导结构域是阳离子蛋白转导结构域。 更优选地，阳离子蛋白转导结构域是非精氨酸，多层膜包括聚电解质多层。 当将组合物提供给细胞时，多层膜在生理介质中溶解或侵蚀，并将分子递送至细胞中。
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公开(公告)号：US20080020942A1
公开(公告)日：2008-01-24
申请号：US11781838
申请日：2007-07-23
申请人： Ronald T. Raines , Jeet Kalia
发明人： Ronald T. Raines , Jeet Kalia
CPC分类号： C07K1/1077 , C07K1/047 , C07K1/13
摘要： Methods and reagents for site-selective functionalization of peptides and proteins. The methods most generally involve the reaction of a thioester with hydrazine. Reagents include bifunctional reagents of formula: H2N—NH—CH2-M-L-FG and salts thereof where M is a single bond or a chemical group carrying a non-bonding electron pair, such as —C(O)NR′—, where R′ is H, or an alkyl or aryl group; L is an optional linker group as described above; and FG is a functional group having reactivity that is orthongonal to that of the hydrazine group. FG can, among others, be an azide, alkenyl, alkynyl, nitrile (—CN) or triazole group and is preferably an azide group (—N3). Methods and reagents can, for example, be combined with intein-mediated protein splicing to link proteins or fragments thereof to various chemical species or to a surface. Surface immobilization of proteins via the methods herein results in immobilized proteins which substantially retain biological activity and is thus useful for the generation of peptide or protein microarrays. Kits for functionalization and/or immobilization of peptides and proteins are provided as well as microarrays of peptides, proteins or both.
摘要翻译： 用于肽和蛋白质的位点选择性功能化的方法和试剂。 该方法最通常涉及硫酯与肼的反应。 试剂包括下式的双官能试剂：<？in-line-formula description =“In-line Formulas”end =“lead”？> H 2 N-NH-CH 2 > -ML-FG <？in-line-formula description =“In-line Formulas”end =“tail”？>及其盐，其中M是单键或携带非键电子对的化学基团，例如 -C（O）NR'-，其中R'是H，或烷基或芳基; L是如上所述的任选的连接基团; 并且FG是具有与肼基团的反应性相反的反应性的官能团。 FG可以是叠氮化物，烯基，炔基，腈（-CN）或三唑基，并且优选为叠氮基（-N 3/3）。 方法和试剂可以例如与内蛋白介导的蛋白质剪接结合，将蛋白质或其片段连接到各种化学物质或表面。 通过本文方法的蛋白质的表面固定产生了基本上保持生物活性并因此可用于产生肽或蛋白质微阵列的固定化蛋白质。 提供肽和蛋白质的功能化和/或固定化试剂盒以及肽，蛋白质或两者的微阵列。
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公开(公告)号：US07122521B2
公开(公告)日：2006-10-17
申请号：US10874725
申请日：2004-06-23
CPC分类号： C07K5/0827 , A61K38/00 , C07K14/001 , C07K14/78
摘要： A novel collagen mimic comprising a tripeptide unit having the formula (flpYaaGly)n, where flp is 4(S)-fluoro-L-proline, is disclosed. The collagen mimic has increased stability relative to the collagen-related triple helices (ProYaaGly)n, (hypYaaGly)n, and (HypYaaGly)n.
摘要翻译： 公开了一种新颖的胶原模拟物，其包含具有式（flpYaaGly）N 3的三肽单元，其中flp是4（S） - 氟-L-脯氨酸。 胶原蛋白模拟物相对于胶原相关的三重螺旋（ProYaaGly），（hypYaaGly）N和/或（HypYaaGly）N 。
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公开(公告)号：US09234048B2
公开(公告)日：2016-01-12
申请号：US13745737
申请日：2013-01-18
申请人： Ronald T. Raines , Gregory Ellis , Michael Palte
发明人： Ronald T. Raines , Gregory Ellis , Michael Palte
CPC分类号： C12N9/2462 , A61K47/54 , C07F5/025 , C12N9/22 , C12Y301/27005 , C12Y302/01017
摘要： Methods for enhancing cellular uptake of cargo molecules by boronating the cargo molecule, particularly with one or more phenylboronic acid groups. Cellular uptake includes at least partial uptake into the cytosol. Boronation includes ligating, crosslinking or otherwise bonding one or more phenylboronic acids substituted to contain a reactive group to a cargo molecule. Boronation also includes ligating, crosslinking or otherwise bonding a phenylboronated oligopeptide to a cargo molecule. The phenylboronate groups are optionally conjugated to the cargo molecule via linking moieties that can be selectively cleaved, such cleavable linkers can allow the phenylboronate groups to be removed from the cargo molecule after the boronated cargo molecule is introduced into the cell. The invention includes certain phenylboronates which are boronation reagents, certain boronated oligopeptides and certain boronated peptides and proteins. The invention also includes kits for enhancing cellular uptake of cargo molecules by boronation with one or more phenylboronates or boronated oligopeptides.
摘要翻译： 通过将货物分子，特别是与一个或多个苯基硼酸基团进行硼化来增强货物分子的细胞吸收的方法。 细胞摄取包括至少部分摄入胞质溶胶。 硼化包括连接，交联或以其他方式将一个或多个被取代以含有反应性基团的苯基硼酸与货物分子结合。 硼化还包括将苯基硼化寡肽与货物分子结合，交联或以其它方式结合。 苯硼酸酯基团任选地通过可以选择性切割的连接部分缀合到货物分子，这种可切割接头可以在硼化货物分子被引入细胞后允许苯基硼酸酯基团从货物分子中除去。 本发明包括某些苯硼氢化物，其为硼化试剂，某些硼化寡肽和某些硼化肽和蛋白质。 本发明还包括用于通过硼化与一种或多种苯基硼酸盐或硼化寡肽来增强货物分子的细胞摄取的试剂盒。
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