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    Insulinotropic peptide synthesis using solid and solution phase combination techniques
    1.
    发明授权
    Insulinotropic peptide synthesis using solid and solution phase combination techniques 失效
    使用固相和溶液相组合技术的胰岛素肽合成

    公开(公告)号：US08227571B2

    公开(公告)日：2012-07-24

    申请号：US12316309

    申请日：2008-12-11

    Applicant: Lin Chen ,  Yeun-Kwei Han ,  Christopher R. Roberts

    Inventor： Lin Chen ,  Yeun-Kwei Han ,  Christopher R. Roberts

    IPC: C07K14/00

    CPC classification number: C07K14/605

    Abstract: The present invention relates to the preparation of insulinotropic peptides that are synthesized using a solid and solution phase (“hybrid”) approach. Generally, the approach includes synthesizing three different peptide intermediate fragments using solid phase chemistry. Solution phase chemistry is then used to add additional amino acid material to the third fragment which is then coupled to the second fragment and then the first fragment in solution. Alternatively, a different second fragment is coupled to the first fragment in the solid phase. Then, solution phase chemistry is then used to add additional amino acid material to a different third fragment. Subsequently, this different third fragment is coupled to the coupled first and different second fragment in the solution phase. The use of a pseudoproline in one of the fragments eases solid phase synthesis of that fragment and also eases subsequent solution phase coupling of this fragment to the other fragments. The present invention is very useful for forming insulinotropic peptides such as GLP-1(7-36) and its natural and non-natural counterparts.

    Abstract translation: 本发明涉及使用固相和溶液相（“混合”）方法合成的促胰岛素肽的制备。 通常，该方法包括使用固相化学合成三种不同的肽中间体片段。 然后使用溶液相化学为第三片段添加另外的氨基酸材料，然后将其与第二片段偶联，然后与溶液中的第一片段偶联。 或者，不同的第二片段与固相中的第一片段偶联。 然后，然后使用溶液相化学法将另外的氨基酸材料添加到不同的第三片段。 随后，将该不同的第三片段与溶液相中的偶联的第一和不同的第二片段偶联。 在其中一个片段中使用假脯氨酸使得该片段的固相合成减轻了该片段随后与其它片段的溶液相偶联。 本发明对于形成促胰岛素肽如GLP-1（7-36）及其天然和非天然对应物非常有用。

    Methods for the synthesis of cyclic peptides
    2.
    发明申请
    Methods for the synthesis of cyclic peptides 审中-公开
    合成环肽的方法

    公开(公告)号：US20080287649A1

    公开(公告)日：2008-11-20

    申请号：US12004265

    申请日：2007-12-20

    Applicant: Lin Chen ,  Yeun-Kwei Han ,  Christopher R. Roberts

    Inventor： Lin Chen ,  Yeun-Kwei Han ,  Christopher R. Roberts

    IPC: C07K2/00 ,  C07C69/616 ,  C07K5/12

    CPC classification number: C07K1/04 ,  C07K5/06113 ,  C07K7/56 ,  C07K14/665

    Abstract: Methods for the synthesis of cyclic peptides are provided, as well as novel dipeptide compounds. The methods include the solid phase synthesis of a dipeptide, which is the coupled to a second peptide in a solid phase reaction. The peptide is then cyclized following the coupling reaction. The methods and dipeptides are particularly useful for the synthesis of MC-4 receptor agonist peptides.

    Abstract translation: 提供了合成环肽的方法，以及新型二肽化合物。 所述方法包括在固相反应中与第二肽偶联的二肽的固相合成。 然后在偶合反应后使肽环化。 该方法和二肽特别可用于合成MC-4受体激动剂肽。

    Process and systems for recovery of peptides
    3.
    发明申请
    Process and systems for recovery of peptides 有权
    用于回收肽的方法和系统

    公开(公告)号：US20050165216A1

    公开(公告)日：2005-07-28

    申请号：US11021845

    申请日：2004-12-23

    Applicant: Yeun-Kwei Han ,  Hiralal Khatri ,  Robert Topping

    Inventor： Yeun-Kwei Han ,  Hiralal Khatri ,  Robert Topping

    IPC: C07K1/02 ,  C07K1/30 ,  C07K14/16

    CPC classification number: C07K14/005 ,  C07K1/30 ,  C12N2740/16122 ,  Y02P20/55

    Abstract: The invention provides methods of obtaining a peptide that include steps of synthesizing a peptide intermediate having one or more side chain protecting groups; providing a solvent to the peptide intermediate to form a peptide intermediate composition; and providing a precipitating agent in an amount sufficient to precipitate the peptide intermediate from the peptide intermediate composition, wherein the precipitating agent is an alcohol having three or more carbon atoms. Also provided are methods for precipitating peptides, methods for concentration peptides, and methods for filtering peptides.

    Abstract translation: 本发明提供了获得肽的方法，其包括合成具有一个或多个侧链保护基团的肽中间体的步骤; 向所述肽中间体提供溶剂以形成肽中间体组合物; 并提供足以使肽中间体从肽中间体组合物沉淀的沉淀剂，其中沉淀剂是具有三个或更多个碳原子的醇。 还提供了沉淀肽的方法，浓缩肽的方法和肽过滤方法。

    Preparation of acyclovir using 1,3 dioxolane
    5.
    发明授权
    Preparation of acyclovir using 1,3 dioxolane 失效
    使用1,3-二氧戊环制备无环鸟苷

    公开(公告)号：US5567816A

    公开(公告)日：1996-10-22

    申请号：US426005

    申请日：1995-04-27

    Applicant: George C. Schloemer ,  Yeun-Kwei Han ,  Peter J. Harrington

    Inventor： George C. Schloemer ,  Yeun-Kwei Han ,  Peter J. Harrington

    IPC: C07D473/00 ,  C07D473/18

    CPC classification number: C07D473/00

    Abstract: A process for the preparation of acyclovir includes contacting an at least partially silylated guanine or mixture of at least partially silylated guanines with 1,3-dioxolane in the presence of a selective alkylation catalyst selected from the group consisting of trifluoromethanesulfonic acid, trimethylsilyl trifluoromethanesulfonate, and bistrimethylsilyl sulfonate, and hydrolyzing the product thus formed.

    Abstract translation: 制备无环鸟苷的方法包括在选自烷基化催化剂的存在下使至少部分甲硅烷基化的鸟嘌呤或至少部分甲硅烷化的鸟嘌呤的混合物与1,3-二氧戊环接触，所述选择性烷基化催化剂选自三氟甲磺酸，三氟甲磺酸三甲基甲硅烷基酯和 双三甲基甲硅烷基磺酸盐，并水解由此形成的产物。

    INSULINOTROPIC PEPTIDE SYNTHESIS USING SOLID AND SOLUTION PHASE COMBINATION TECHNIQUES
    6.
    发明申请
    INSULINOTROPIC PEPTIDE SYNTHESIS USING SOLID AND SOLUTION PHASE COMBINATION TECHNIQUES 审中-公开
    使用固相和溶液相组合技术的胰岛素肽合成

    公开(公告)号：US20100292435A1

    公开(公告)日：2010-11-18

    申请号：US12770907

    申请日：2010-04-30

    Applicant: LIN CHEN ,  YEUN-KWEI HAN ,  CHRISTOPHER R. ROBERTS

    Inventor： LIN CHEN ,  YEUN-KWEI HAN ,  CHRISTOPHER R. ROBERTS

    IPC: C07K14/00 ,  C07K7/08

    CPC classification number: C07K14/605

    Abstract: The present invention relates to the preparation of insulinotropic peptides that are synthesized using a solid and solution phase (“hybrid”) approach. Generally, the approach includes synthesizing three different peptide intermediate fragments using solid phase chemistry. Solution phase chemistry is then used to couple the second fragment and the first fragment. Alternatively, a different second fragment is coupled to a first fragment in the solid phase. Then, solution phase chemistry is then used to add the third fragment, whereby the third fragment is coupled to the coupled first and second fragments in the solution phase. The present invention is very useful for forming insulinotropic peptides such as GLP-1(7-36) and its natural and non-natural counterparts.

    Abstract translation: 本发明涉及使用固相和溶液相（“混合”）方法合成的促胰岛素肽的制备。 通常，该方法包括使用固相化学合成三种不同的肽中间体片段。 然后使用溶液相化学来偶联第二个片段和第一个片段。 或者，不同的第二片段与固相中的第一片段偶联。 然后，然后使用溶液相化学添加第三片段，由此第三片段与溶液相中的偶联第一片段和第二片段偶联。 本发明对于形成促胰岛素肽如GLP-1（7-36）及其天然和非天然对应物非常有用。

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