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    • 6. 发明申请
    • STABILIZATION OF THE COLLAGEN TRIPLE HELIX BY O-METHYLATION OF HYDROXYPROLINE RESIDUES
    • 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
    • US20090264626A1
    • 2009-10-22
    • US12367374
    • 2009-02-06
    • Ronald T. RainesFrank W. Kotch
    • Ronald T. RainesFrank W. Kotch
    • C07K14/78
    • C07K14/78
    • 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.
    • 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。
    • 8. 发明申请
    • Reagents and Methods for Appending Functional Groups to Proteins
    • 将功能组附加到蛋白质的试剂和方法
    • US20080020942A1
    • 2008-01-24
    • US11781838
    • 2007-07-23
    • Ronald T. RainesJeet Kalia
    • Ronald T. RainesJeet Kalia
    • C40B50/18C07K1/113C07K17/06C40B40/10
    • C07K1/1077C07K1/047C07K1/13
    • 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.
    • 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。
    • 10. 发明授权
    • Boronate-mediated delivery of molecules into cells
    • 硼酸盐介导的分子进入细胞
    • US09234048B2
    • 2016-01-12
    • US13745737
    • 2013-01-18
    • Ronald T. RainesGregory EllisMichael Palte
    • Ronald T. RainesGregory EllisMichael Palte
    • A61K47/48C07K19/00C07F5/02
    • C12N9/2462A61K47/54C07F5/025C12N9/22C12Y301/27005C12Y302/01017
    • 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.
    • 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。