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    Peptide synthesis method and solid support for use in the method
    1.
    发明授权
    Peptide synthesis method and solid support for use in the method 失效
    肽合成方法和固体支持用于该方法

    公开(公告)号：US5373053A

    公开(公告)日：1994-12-13

    申请号：US990584

    申请日：1992-12-14

    申请人： Rolf H. Berg ,  Kristoffer Almdal ,  Walther B. Pedersen ,  Arne Holm ,  James P. Tam ,  Robert B. Merrifield

    发明人： Rolf H. Berg ,  Kristoffer Almdal ,  Walther B. Pedersen ,  Arne Holm ,  James P. Tam ,  Robert B. Merrifield

    IPC分类号： C07K1/04 ,  G01N33/545 ,  C07C103/52 ,  C07D51/52

    CPC分类号： G01N33/545 ,  C07K1/042

    摘要： A method for the solid-phase synthesis of peptides or proteins in high yield and high purity uses a solid support consisting of a functionalized polystyrene-grafted polymer substrate, the grafted polystyrene chains being substantially non-cross-linked and having a chain molecular weight, not including optional non-reactive substituents, of at least 200,000, preferably in the range of 600,000-1,200,000. Particularly suitable polymer substrates are substrates of a polyolefin such as polyethylene. The method is particularly well-suited to the compartmentalized synthesis of a multitude of peptides or proteins in a parallel and substantially simultaneous fashion.Preferred embodiments of a solid support for performing the synthesis are prepared from thin polyethylene sheet or film which has been grafted with polystyrene chains in a radical-initiated process in which the polyethylene sheet or film is immersed in a solution of optionally substituted styrene monomer in an alcohol such as methanol, the volume percentage of styrene in the solution preferably being about 30% v/v, and subjected to gamma irradiation.

    摘要翻译： 以高产率和高纯度固相合成肽或蛋白质的方法使用由官能化聚苯乙烯接枝的聚合物基质组成的固体支持物，所述接枝聚苯乙烯链基本上是非交联并具有链分子量， 不包括任选的非反应性取代基，为至少20万，优选在600,000-1200,000的范围内。 特别合适的聚合物基材是聚烯烃如聚乙烯的基材。 该方法特别适合于以平行和基本上同时的方式区分多种肽或蛋白质的合成。 用于进行合成的固体支持物的优选实施方案由在自由基引发的方法中已经用聚苯乙烯链接枝的薄聚乙烯片或薄膜制备，其中聚乙烯片或薄膜浸渍在任选取代的苯乙烯单体的溶液中 醇如甲醇，溶液中苯乙烯的体积百分比优选为约30％v / v，并进行γ照射。

    Peptide synthesis method and solid support for use in the method
    2.
    发明授权
    Peptide synthesis method and solid support for use in the method 失效
    肽合成方法和固体支持用于该方法

    公开(公告)号：US5258454A

    公开(公告)日：1993-11-02

    申请号：US882059

    申请日：1992-05-12

    申请人： Rolf H. Berg ,  Kristoffer Almdal ,  Walther B. Pedersen ,  Arne Holm ,  James P. Tam ,  Robert B. Merrifield

    发明人： Rolf H. Berg ,  Kristoffer Almdal ,  Walther B. Pedersen ,  Arne Holm ,  James P. Tam ,  Robert B. Merrifield

    IPC分类号： C07K1/04 ,  G01N33/545 ,  C08F283/00 ,  C08G63/48 ,  C08G63/91

    CPC分类号： G01N33/545 ,  C07K1/042

    摘要： A method for the solid-phase synthesis of peptides or proteins in high yield and high purity uses a solid-support consisting of a functionalized polystyrene-grafted polymer substrate, the grafted polystyrene chains being substantially non-cross-linked and having a chain molecular weight, not including optional non-reactive substituents, of at least 200,000, preferably in the range of 600,000-1,200,000. Particularly suitable polymer substrates are substrates of a polyolefin such as polyethylene. The method is particularly well-suited to the compartmentalized synthesis of a multitude of peptides or proteins in a parallel and substantially simultaneous fashion.Preferred embodiments of a solid support for performing the synthesis are prepared from thin polyethylene sheet or film which has been grafted with polystyrene chains in a radical-initiated process in which the polyethylene sheet or film is immersed in a solution of optionally substituted styrene monomer in an alcohol such as methanol, the volume percentage of styrene in the solution preferably being about 30% v/v, and subjected to gamma irradiation.

    摘要翻译： 用于以高产率和高纯度固相合成肽或蛋白质的方法使用由官能化聚苯乙烯接枝的聚合物基质组成的固体支持物，所述接枝聚苯乙烯链基本上是非交联的且具有链分子量 ，不包括任选的非反应性取代基，为至少20万，优选在600,000-1200,000的范围内。 特别合适的聚合物基材是聚烯烃如聚乙烯的基材。 该方法特别适合于以平行和基本上同时的方式区分多种肽或蛋白质的合成。 用于进行合成的固体支持物的优选实施方案由在自由基引发的方法中已经用聚苯乙烯链接枝的薄聚乙烯片或薄膜制备，其中聚乙烯片或薄膜浸渍在任选取代的苯乙烯单体的溶液中 醇如甲醇，溶液中苯乙烯的体积百分比优选为约30％v / v，并进行γ照射。

    Peptide synthesis reagents and method of use
    3.
    发明授权
    Peptide synthesis reagents and method of use 失效
    肽合成试剂及其使用方法

    公开(公告)号：US4507230A

    公开(公告)日：1985-03-26

    申请号：US377443

    申请日：1982-05-12

    申请人： James P. Tam ,  William F. Heath, Jr. ,  Robert B. Merrifield

    发明人： James P. Tam ,  William F. Heath, Jr. ,  Robert B. Merrifield

    IPC分类号： C07K1/04 ,  C07K1/12 ,  C07K14/605 ,  C07C103/52 ,  C08L89/00

    CPC分类号： C07K14/605 ,  C07K1/042 ,  C07K1/12

    摘要： A method of releasing a functional group present in an amino acid or amino acyl residue from a resin or protecting residue which is bonded to the functional group by a linkage having proton affinity, which comprises: reacting the functional group bonded to the organic residue, with a mixture of HF and a base for a time and under conditions effective to produce the release; wherein the amounts of HF and base in the mixture are adjusted so that said release occurs substantially by an S.sub.N 2 mechanism.

    摘要翻译： 通过具有质子亲合力的键从树脂或保护残基中释放存在于氨基酸或氨基酰基残基中的官能团的方法，该方法包括：使与有机残基键合的官能团与 在有效产生释放的时间和条件下，HF和碱的混合物; 其中调节混合物中HF和碱的量，使得所述释放基本上由SN2机制发生。

    Oxidative folding of peptide and protein substrates using hydrocarbon sulfoxides
    4.
    发明授权
    Oxidative folding of peptide and protein substrates using hydrocarbon sulfoxides 失效
    使用烃类亚砜氧化折叠肽和蛋白质底物

    公开(公告)号：US5144006A

    公开(公告)日：1992-09-01

    申请号：US714659

    申请日：1991-06-13

    申请人： James P. Tam

    发明人： James P. Tam

    IPC分类号： C07K1/113

    CPC分类号： C07K1/1133

    摘要： Method for oxidative folding of peptide and protein substrates to form disulfide bonds using dimethyl sulfoxide and other equivalent sulfoxides as mild oxidizing agents.

    摘要翻译： 使用二甲亚砜和其他等同的亚砜作为温和氧化剂的肽和蛋白底物的氧化折叠形成二硫键的方法。

    Method for synthesis of proteins
    5.
    发明授权
    Method for synthesis of proteins 失效
    蛋白质合成方法

    公开(公告)号：US06310180B1

    公开(公告)日：2001-10-30

    申请号：US08492411

    申请日：1995-06-19

    申请人： James P. Tam

    发明人： James P. Tam

    IPC分类号： A61K3800

    CPC分类号： G01N33/531 ,  A61K38/00 ,  C07K1/08 ,  C07K1/1075 ,  C07K1/1077 ,  C07K7/64 ,  C07K14/005 ,  C12N2740/13022 ,  C12N2740/16222 ,  Y02P20/55

    摘要： A method for peptide synthesis is disclosed that requires neither protecting groups nor activation of the C-&agr; carboxyl groups. The method comprises ligating a first molecule to a second molecule by promoting the orthogonal coupling of the molecules to each other. In an aspect of this method, an acyl-type reaction occurs between the molecules. The method contemplates the joining of molecules of variant size to each other, as well as the coupling of multiple identical molecules. The invention also covers the ligation of unprotected peptide, proteins or nonpeptide segments to prepare therapeutic products and synthetic vaccines with linear, circularized, or branched backbone structures, as well as the site-specific modification of peptides or proteins by lipidation and pegylation.

    摘要翻译： 公开了一种肽合成方法，既不需要保护基团也不需要C-α羧基基团的活化。 该方法包括通过促进分子彼此的正交偶联将第一分子连接到第二分子。 在该方法的一个方面，在分子之间发生酰基型反应。 该方法考虑了将变体大小的分子彼此连接以及多个相同分子的偶联。 本发明还涵盖未保护的肽，蛋白质或非肽段的连接以制备治疗产物和具有线性，环化或支化骨架结构的合成疫苗，以及通过脂化和聚乙二醇化进行肽或蛋白质的位点特异性修饰。

    Preparation and use of ginsentides and ginsentide-like peptides
    6.
    发明授权
    Preparation and use of ginsentides and ginsentide-like peptides 有权

    公开(公告)号：US11174298B2

    公开(公告)日：2021-11-16

    申请号：US16348770

    申请日：2017-11-09

    申请人： James P. Tam

    发明人： James P. Tam

    IPC分类号： C07K14/415 ,  A61P7/02 ,  C07K14/00 ,  A61K38/00

    摘要： The present invention relates to the methods of solid-phase peptide synthesis or recombinant production of ginsentide or ginsentide-like peptides or salts thereof. Further provided are uses of the ginsentide or ginsentide-like peptides or salts thereof as α1-adrenergic receptor antagonists and vasorelaxants, nitric oxide-boosting agents, anti-thrombotic agents, anti-atherosclerotic agents, as protective agents against doxorubicin-induced cardiotoxicity, anti-ageing and adaptogenic agents, nutraceuticals, health supplements, or cosmetic ingredients.

    Multiple antigen peptide system having adjuvant properties, vaccines prepared therefrom and methods of use thereof
    8.
    发明授权
    Multiple antigen peptide system having adjuvant properties, vaccines prepared therefrom and methods of use thereof 失效
    具有佐剂性质的多抗原肽系统，由其制备的疫苗及其使用方法

    公开(公告)号：US5580563A

    公开(公告)日：1996-12-03

    申请号：US331489

    申请日：1994-12-28

    申请人： James P. Tam

    发明人： James P. Tam

    IPC分类号： A61K39/00 ,  A61K39/385 ,  C07K14/16 ,  C07K19/00 ,  A61K39/39 ,  A61K9/127 ,  A61K39/02

    CPC分类号： C07K14/005 ,  A61K39/385 ,  C07K19/00 ,  A61K2039/55555 ,  A61K2039/645 ,  A61K39/00 ,  C12N2740/16122 ,  Y10S424/16 ,  Y10S977/754 ,  Y10S977/917

    摘要： A multiple antigenic peptide system is disclosed that comprises a dendritic core and peptide and a lipophilic anchoring moiety. This particular combination has as an advantage that it eliminates the need for the inclusion of adjuvants found to be toxic to humans, and facilitates the exponential amplification of the antigenic potential of a vaccine prepared therefrom, as noncovalent amplification by a liposome or micellar form is possible. Further, multiple different antigenic peptides may be attached so that the system may be prepared for administration to concurrently treat diverse ailments, such as for example, AIDS and influenza. The present multiple antigen peptide system is capable of eliciting an immune response when injected into a mammal, and accordingly, vaccines prepared from the system and methods of use including therapeutic protocols are included.

    摘要翻译： PCT No.PCT / US93 / 04179 Sec。 371日期1994年12月28日第 102（e）日期1994年12月28日PCT提交1993年5月3日PCT公布。 公开号WO93 / 22343 日期：1993年11月11日公开了包含树突核心和肽和亲脂性锚定部分的多重抗原肽系统。 这种特殊的组合具有这样的优点：它消除了对发现对人有毒性的佐剂的需要，并且有助于由其制备的疫苗的抗原性潜力的指数扩增，因为通过脂质体或胶束形式的非共价扩增是可能的 。 此外，可以连接多种不同的抗原肽，使得该系统可以被制备用于施用以同时治疗多种疾病，例如AIDS和流感。 本发明的多抗原肽系统能够在注射到哺乳动物中时引发免疫应答，因此，包括从系统制备的疫苗和包括治疗方案的使用方法。

    Litigation of sidechain unprotected peptides via a masked glycoaldehyde ester and O,N-acyl rearrangement
    10.
    发明授权
    Litigation of sidechain unprotected peptides via a masked glycoaldehyde ester and O,N-acyl rearrangement 失效
    通过掩蔽的糖醛酸酯和O，N-酰基重排对侧链未保护的肽进行诉讼

    公开(公告)号：US5589356A

    公开(公告)日：1996-12-31

    申请号：US81412

    申请日：1993-06-21

    申请人： James P. Tam

    发明人： James P. Tam

    IPC分类号： A61K38/00 ,  C07K1/08 ,  C07K1/107 ,  C07K7/64 ,  C07K14/15 ,  C07K14/16 ,  G01N33/531 ,  C12P21/06 ,  C07K1/00

    CPC分类号： C07K14/005 ,  C07K1/08 ,  C07K1/1075 ,  C07K1/1077 ,  C07K7/64 ,  G01N33/531 ,  A61K38/00 ,  C12N2740/13022 ,  C12N2740/16222 ,  Y02P20/55

    摘要： A method of chemical ligation of peptides that requires no side chain protecting groups and no activation of the C-.alpha. carboxyl group is presented. The method consists of three steps. In the first step, initiation, a masked glycoaldehyde ester is enzymatically or chemically coupled to the C-terminal carboxylic acid of an sidechain unprotected first peptide. In the second step, ring formation, the masked aldehyde ester of the first peptide is unmasked, and then reacted with the N-.alpha. amino acid of a second sidechain unprotected peptide to form a ring structure. In the third step, rearrangement, the O-acyl ester linkage transfers at higher pH to an N-acyl linkage on the ring to form a peptide bond.

    摘要翻译： 提出了不需要侧链保护基团并且不活化C-α-羧基的肽的化学连接方法。 该方法由三个步骤组成。 在第一步骤中，掩蔽的糖醛酸酯被酶或化学偶联至侧链未保护的第一肽的C-末端羧酸。 在第二步中，形成环，第一肽的被掩蔽的醛酯被掩蔽，然后与第二侧链未保护肽的N-α氨基酸反应形成环结构。 在第三步中，重排，O-酰基酯键在较高pH下转移至环上的N-酰基键形成肽键。