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    Spatially aligned conjugated composition having a thioether bond linkage
    1.
    发明授权
    Spatially aligned conjugated composition having a thioether bond linkage 失效
    具有硫醚键的空间取向的共轭组合物

    公开(公告)号：US6086881A

    公开(公告)日：2000-07-11

    申请号：US79374

    申请日：1998-05-15

    申请人： Andreas Frey ,  Marian R. Neutra ,  Frank A. Robey

    发明人： Andreas Frey ,  Marian R. Neutra ,  Frank A. Robey

    IPC分类号： A61K9/16 ,  A61K9/51 ,  A61K39/385 ,  A61P37/04 ,  C07K14/16 ,  A61K38/00 ,  A61M36/14 ,  C07K5/00

    CPC分类号： C07K14/005 ,  A61K39/385 ,  A61K2039/55505 ,  A61K2039/60 ,  A61K2039/627 ,  C12N2740/16122

    摘要： The present invention is a spatially aligned conjugated composition which comprises at least one chemically modified substance which is immunologically representative of a prechosen infectious agent and provides a chemical constituent for entering into and forming a thioether bond; a plurality of chemically substituted metallic oxide particles which range from about 10-10,000 nanometers and are able to enter into a thioether bond and covalent linkage; and at least one thioether bond and linkage joining the metallic oxide particles in a controlled and spatially aligned manner to the antigen or hapten. The conjugated composition may be alternatively employed as an immunogen; as a vaccine; as a diagnostic tool and reactant; and as an analytical material suitable for testing the pharmacological activity of new compounds.

    摘要翻译： 本发明是空间取向的共轭组合物，其包含至少一种化学修饰的物质，其具有免疫学上代表预先感染的物质并提供用于进入和形成硫醚键的化学成分; 多个化学取代的金属氧化物颗粒，其范围为约10-10,000纳米，并且能够进入硫醚键和共价键; 以及至少一个硫醚键和连接金属氧化物颗粒的控制和空间对准方式与抗原或半抗原的连接。 共轭组合物可以替代地用作免疫原; 作为疫苗; 作为诊断工具和反应物; 并且作为适用于测试新化合物的药理活性的分析物质。

    Amino acid derivative and bromoacetyl modified peptides for the preparation of synthetic peptide polymers, conjugated peptides, and cyclic peptides
    3.
    发明授权
    Amino acid derivative and bromoacetyl modified peptides for the preparation of synthetic peptide polymers, conjugated peptides, and cyclic peptides 失效
    用于制备合成肽聚合物，缀合肽和环肽的氨基酸衍生物和溴乙酰基修饰的肽

    公开(公告)号：US5286846A

    公开(公告)日：1994-02-15

    申请号：US715650

    申请日：1991-06-14

    申请人： John K. Inman ,  Frank A. Robey

    发明人： John K. Inman ,  Frank A. Robey

    IPC分类号： A61K47/48 ,  C07C271/22 ,  C07K1/00 ,  C07K1/04 ,  C07K1/107 ,  A61K37/02 ,  C08G63/48

    CPC分类号： A61K47/48238 ,  C07C271/22 ,  C07K1/006 ,  C07K1/04 ,  C07K1/1077

    摘要： A new amino derivative, N.sup..alpha. -tert-butoxycarbonyl-N.sup..epsilon. -(N-bromoacetyl-.beta.-alanyl)-L-lysine (BBAL), has been synthesized as a reagent to be used in solid-phase peptide synthesis for introducing a side-chain bromoacetyl group at any desired position in a peptide sequence. The bromoacetyl group subsequently serves as a sulfhydryl-selective cross-linking function for the preparation of cyclic peptides, peptide conjugates and polymers. BBAL residues are stable to final HF deprotection/cleavage. BBAL peptides can be directly coupled to other molecules or surfaces which possess free sulfhydryl groups by forming stable thioether linkages. Peptides containing both BBAL and cysteine residues can be self-coupled to produce either cyclic molecules or linear peptide polymers. Such peptide derivatives are useful in preparing potential peptide immunogens, vaccines and therapeutics, and for substances such as peptides linked to polymers, plastics, enamels and ceramics.

    摘要翻译： 已经合成了一种新的氨基酸衍生物，N - 叔丁氧羰基-Nε-（N-溴乙酰基-β-丙氨酰基）-L-赖氨酸（BBAL）作为固相中的试剂 用于在肽序列中的任何所需位置引入侧链溴乙酰基的肽合成。 随后溴乙酰基用作制备环肽，肽缀合物和聚合物的巯基选择性交联功能。 BBAL残基对最终的HF去保护/切割是稳定的。 BBAL肽可以通过形成稳定的硫醚键直接偶联到具有游离巯基的其它分子或表面。 含有BBAL和半胱氨酸残基的肽可以是自偶联的，以产生环状分子或线性肽聚合物。 这样的肽衍生物可用于制备潜在的肽免疫原，疫苗和治疗剂，以及用于物质如与聚合物，塑料，搪瓷和陶瓷连接的肽。

    Cell attachment peptides derived from amyloid P component
    4.
    发明授权
    Cell attachment peptides derived from amyloid P component 失效
    衍生自淀粉样蛋白P成分的细胞附着肽

    公开(公告)号：US5092876A

    公开(公告)日：1992-03-03

    申请号：US400870

    申请日：1989-08-30

    申请人： Subhash Dhawan ,  Frank A. Robey

    发明人： Subhash Dhawan ,  Frank A. Robey

    IPC分类号： A61K38/00 ,  A61L27/34 ,  C07K14/47 ,  C12N5/00

    CPC分类号： C07K14/4711 ,  A61L27/34 ,  C12N5/0068 ,  A61K38/00 ,  C12N2533/50

    摘要： The present invention is directed to a human serum amyloid P component peptide sequence having 12 ammo acid residues and having the sequence identified as Glu-Lys-Pro-Leu-Gln-Asn-Phe-Thr-Leu-Cys-Phe-Arg. The invention is also directed to fragments of the above peptide. Two fragments useful in the present invention have the sequence Phe-Thr-Leu-Cys-Phe-Arg and Leu-Cys-Phe-Arg. The above peptides are useful for attaching cells to substrates such as ceramics, tissue culture, dishes, polymers or enamels and thus are useful as research tools for studying particular cells. The above peptides are also useful in vivo as artificial organ replacements which attach surrounding natural cells.

    摘要翻译： 本发明涉及具有12个氨基酸残基且具有鉴定为Glu-Lys-Pro-Leu-Gln-Asn-Phe-Thr-Leu-Cys-Phe-Arg的序列的人血清淀粉样蛋白P组分肽序列。 本发明还涉及上述肽的片段。 在本发明中有用的两个片段具有序列Phe-Thr-Leu-Cys-Phe-Arg和Leu-Cys-Phe-Arg。 上述肽可用于将细胞附着到诸如陶瓷，组织培养，培养皿，聚合物或搪瓷等底物上，因此可用作研究特定细胞的研究工具。 上述肽在体内也可用作附着周围天然细胞的人造器官替代物。

    Synthesis of chloroacetyl and bromoacetyl modified peptides for the preparation of synthetic peptide polymers, conjugated peptides, and cyclic peptides
    5.
    发明授权
    Synthesis of chloroacetyl and bromoacetyl modified peptides for the preparation of synthetic peptide polymers, conjugated peptides, and cyclic peptides 失效
    用于制备合成肽聚合物，缀合肽和环肽的氯乙酰基和溴乙酰基修饰肽的合成

    公开(公告)号：US5066716A

    公开(公告)日：1991-11-19

    申请号：US283849

    申请日：1988-12-13

    申请人： Frank A. Robey ,  Raymond L. Fields ,  Wolfgang Lindner

    发明人： Frank A. Robey ,  Raymond L. Fields ,  Wolfgang Lindner

    IPC分类号： C07K1/107

    CPC分类号： C07K1/1077

    摘要： A method to incorporate bromoacetyl and chloroacetyl moieties on amino groups of synthetic peptides using a standard program with an automated peptide synthesizer has been developed. The bromoacetyl and chloroacetyl-derivatized peptides react well with sulfhydryl-containing proteins and with peptides containing cysteine residues. Autopolymerization or cyclization occurs by reaction of the free sulfhydryl of cysteine in a peptide with the bromoacetyl group (or chloroacetyl group) and reactions can generally be controlled by controlling the concentrations of starting peptide in neutral pH buffers. Analytical methods for evaluating the polymers or cyclized peptides include gel filtration chromatography, reverse phase HPLC, SDS-PAGE and amino acid analysis where the degree of reaction can be evaluated by quantifying the amount of S-carboxymethylcysteine formed after HCl hydrolysis. N-bromoacetyl-derivatized peptides are useful as reagents for potential peptide immunogens, vaccines and therapeutics, and for substances such as peptides linked to polymers, plastics, enamels, and ceramics.

    摘要翻译： 已经开发了使用具有自动化肽合成仪的标准程序将溴乙酰基和氯乙酰部分并入合成肽的氨基上的方法。 溴乙酰基和氯乙酰基衍生的肽与含巯基的蛋白质和含有半胱氨酸残基的肽反应良好。 通过肽中半胱氨酸的游离巯基与溴乙酰基（或氯乙酰基）反应而发生自聚合或环化，通常可以通过控制中性pH缓冲液中起始肽的浓度来控制反应。 用于评估聚合物或环化肽的分析方法包括凝胶过滤层析，反相HPLC，SDS-PAGE和氨基酸分析，其中可以通过定量HCl水解后形成的S-羧甲基半胱氨酸的量来评估反应程度。 N-溴乙酰基衍生的肽可用作潜在的肽免疫原，疫苗和治疗剂的试剂，以及用于与聚合物，塑料，搪瓷和陶瓷连接的肽的物质。

    Amino acid derivative and bromoacetyl modified peptides for the preparation of synthetic peptide polymers, conjugated peptides, and cyclic peptides
    6.
    发明授权
    Amino acid derivative and bromoacetyl modified peptides for the preparation of synthetic peptide polymers, conjugated peptides, and cyclic peptides 失效
    用于制备合成肽聚合物，缀合肽和环肽的氨基酸衍生物和溴乙酰基修饰的肽

    公开(公告)号：US5444150A

    公开(公告)日：1995-08-22

    申请号：US154786

    申请日：1993-11-19

    申请人： John K. Inman ,  Frank A. Robey

    发明人： John K. Inman ,  Frank A. Robey

    IPC分类号： A61K47/48 ,  C07C271/22 ,  C07K1/00 ,  C07K1/04 ,  C07K1/107 ,  A61K38/00 ,  C08G63/48

    CPC分类号： A61K47/48238 ,  C07C271/22 ,  C07K1/006 ,  C07K1/04 ,  C07K1/1077

    摘要： A new amino acid derivative, N.sup..alpha. -tert-butoxycarbonyl-N.sup.e -(N-bromoacetyl-.beta.-alanyl)-L-lysine (BBAL), has been synthesized as a reagent to be used in solid-phase peptide synthesis for introducing a side-chain bromoacetyl group at any desired position in a peptide sequence. The bromoacetyl group subsequently serves as a sulfhydryl-selective cross-linking function for the preparation of cyclic peptides, peptide conjugates and polymers. BBAL residues are stable to final HF deprotection/cleavage. BBAL peptides can be directly coupled to other molecules or surfaces which possess free sulfhydryl groups by forming stable thioether linkages. Peptides containing both BBAL and cysteine residues can be self-coupled to produce either cyclic molecules or linear peptide polymers. Such peptide derivatives are useful in preparing potential peptide immunogens, vaccines and therapeutics, and for substances such as peptides linked to polymers, plastics, enamels and ceramics.

    摘要翻译： 已经合成了新的氨基酸衍生物，Nα-叔丁氧基羰基-Ne-（N-溴乙酰基-β-丙氨酰基）-L-赖氨酸（BBAL）作为用于固相肽合成的试剂，用于引入 侧链溴乙酰基在肽序列中的任何所需位置。 随后溴乙酰基用作制备环肽，肽缀合物和聚合物的巯基选择性交联功能。 BBAL残基对最终的HF去保护/切割是稳定的。 BBAL肽可以通过形成稳定的硫醚键直接偶联到具有游离巯基的其它分子或表面。 含有BBAL和半胱氨酸残基的肽可以是自偶联的，以产生环状分子或线性肽聚合物。 这样的肽衍生物可用于制备潜在的肽免疫原，疫苗和治疗剂，以及用于诸如与聚合物，塑料，搪瓷和陶瓷连接的肽的物质。