公开(公告)号：US07473788B2

公开(公告)日：2009-01-06

申请号：US11634429

申请日：2006-12-05

申请人： Kristian Stromgaard ,  Makiko Suehiro ,  Koji Nakanishi ,  Stine B. Vogensen

发明人： Kristian Stromgaard ,  Makiko Suehiro ,  Koji Nakanishi ,  Stine B. Vogensen

IPC分类号： C07D305/14 ,  A01K43/12

CPC分类号： C07D493/20 ,  C07D493/22

摘要： The subject invention provides compounds having the structure: wherein R1 is H, OH, a photoactivatable moiety, a fluorescent moiety, or a radioactive moiety; R2 is H, OH, a photoactivatable moiety, a fluorescent moiety, or a radioactive moiety; R3 is H or OH; R4 is H, OH, a photoactivatable moiety, a fluorescent moiety, or a radioactive moiety; and wherein at least one of R1, R2, R3, or R4 is a photoactivatable moiety, a fluorescent moiety, or a radioactive moiety, or an optically pure enantiomer of the compound or wherein R1 is H or OH; R2 is H, OH, halogen, unsubstituted or substituted, straight or branched (C1-C5) alkyl group, (C2-C5) alkenyl, or a (C2-C5) alkynyl, (C1-C5) alkoxy, (C2-C5) alkenyloxy, or (C2-C5) alkynyloxy, —N3, —COR5, —CONR5R6, —CO2R5, —OCOR5, —NH(OH), —NR5R6, —NHCOR5, —N(OH)COR5, —CH2OR5, —OCH2CO2R5, —CH2SR5, —CH2NR5R6, —SR5, —OSR5, or —NR5SO2R6, where R5 and R6 are each independently hydrogen, substituted or unsubstituted (C1-C5) alkyl, (C2-C5) alkenyl, or (C2-C5) alkynyl, or a cycloalkyl or aryl group having 3 to 10 carbon atoms; R3 is H or OH; R4 is H, (C1-C10) alkyl, (C1-C10) alkenyl, (C1-C10) alkynyl, -A-Ar, -A-Z-Ar, —SO2—Ar, or -A-NR5, or —R7, where A, Z and Ar are as defined herein, and the use of the compounds for detecting or identifying a receptor which binds the compounds of the invention or for treating a PAF associated condition in a subject.

摘要翻译： 本发明提供具有以下结构的化合物：其中R1是H，OH，可光活化部分，荧光部分或放射性部分; R2是H，OH，可光活化部分，荧光部分或放射性部分; R3是H或OH; R4是H，OH，可光活化部分，荧光部分或放射性部分; 并且其中R 1，R 2，R 3或R 4中的至少一个是所述化合物的可光活化部分，荧光部分或放射性部分或光学纯对映异构体，或其中R 1是H或OH; R2是H，OH，卤素，未取代或取代的直链或支链（C1-C5）烷基，（C2-C5）烯基或（C2-C5）炔基，（C1-C5）烷氧基，（C2-C5 ）烯氧基或（C 2 -C 5）炔氧基，-N 3，-COR 5，-CONR 5 R 6，-CO 2 R 5，-OCOR 5，-NH（OH），-NR 5 R 6，-NHCOR 5，-N（OH）COR 5，-CH 2 OR 5，-OCH 2 CO 2 R 5 ，（C 2 -C 5）烯基或（C 2 -C 5）炔基，其中R 5和R 6各自独立地为氢，取代或未取代的（C 1 -C 5）烷基，（C 2 -C 5） ，或具有3〜10个碳原子的环烷基或芳基; R3是H或OH; R4是H，（C1-C10）烷基，（C1-C10）烯基，（C1-C10）炔基，-A-Ar，-AZ-Ar，-SO2-Ar或-A-NR5或-R7， 其中A，Z和Ar如本文所定义，以及该化合物用于检测或鉴定结合本发明化合物或用于治疗受试者中PAF相关病症的受体的用途。

公开(公告)号：US20070098632A1

公开(公告)日：2007-05-03

申请号：US11634429

申请日：2006-12-05

申请人： Kristian Stromgaard ,  Makiko Suehiro ,  Koji Nakanishi ,  Stine Vogensen

发明人： Kristian Stromgaard ,  Makiko Suehiro ,  Koji Nakanishi ,  Stine Vogensen

IPC分类号： A61K51/00 ,  C12Q1/68 ,  C07F5/00 ,  A61K31/506 ,  A61K31/4433 ,  A61K31/4709 ,  A61K31/396 ,  A61K31/365 ,  C07D493/22 ,  C12N9/00 ,  C07H21/04 ,  G01N33/53 ,  C07K14/705

CPC分类号： C07D493/20 ,  C07D493/22

摘要： The subject invention provides compounds having the structure: wherein R1 is H, OH, a photoactivatable moiety, a fluorescent moiety, or a radioactive moiety; R2 is H, OH, a photoactivatable moiety, a fluorescent moiety, or a radioactive moiety; R3 is H or OH; R4 is H, OH, a photoactivatable moiety, a fluorescent moiety, or a radioactive moiety; and wherein at least one of R1, R2, R3, or R4 is a photoactivatable moiety, a fluorescent moiety, or a radioactive moiety, or an optically pure enantiomer of the compound or wherein R1 is H or OH; R2 is H, OH, halogen, unsubstituted or substituted, straight or branched (C1-C5) alkyl group, (C2-C5) alkenyl, or a (C2-C5) alkynyl, (C1-C5) alkoxy, (C2-C5) alkenyloxy, or (C2-C5) alkynyloxy, —N3, —COR5, —CONR5R6, —CO2R5, —OCOR5, —NH(OH), —NR5R6, —NHCOR5, —N(OH)COR5, —CH2OR5, —OCH2CO2R5, —CH2SR5, —CH2NR5R6, —SR5, —OSR5, or —NR5SO2R6, where R5 and R6 are each independently hydrogen, substituted or unsubstituted (C1-C5) alkyl, (C2-C5) alkenyl, or (C2-C5) alkynyl, or a cycloalkyl or aryl group having 3 to 10 carbon atoms; R3 is H or OH; R4 is H, (C1-C10) alkyl, (C1-C10) alkenyl, (C1-C10) alkynyl, -A-Ar, -A-Z-Ar, —SO2—Ar, or -A-NR5, or —R7, where A, Z and Ar are as defined herein, and the use of the compounds for detecting or identifying a receptor which binds the compounds of the invention or for treating a PAF associated condition in a subject.

公开(公告)号：US06693091B2

公开(公告)日：2004-02-17

申请号：US10109965

申请日：2002-03-29

申请人： Kristian Stromgaard ,  Makiko Suehiro ,  Koji Nakanishi

发明人： Kristian Stromgaard ,  Makiko Suehiro ,  Koji Nakanishi

IPC分类号： A61K3133

CPC分类号： C07D493/20 ,  C07D493/22

摘要： A compound having the structure: wherein R1 is H, OH, a photoactivatable moiety, a fluorescent moiety, or a radioactive moiety; wherein R2 is H, OH, a photoactivatable moiety, a fluorescent moiety, or a radioactive moiety; wherein R3 is H or OH; wherein R4 is H, OH, a photoactivatable moiety, a fluorescent moiety, or a radioactive moiety; and wherein at least one of R1, R2, R3, or R4 is a photoactivatable moiety, a fluorescent moiety, or a radioactive moiety. Optically pure enantiomers and salts of the compound are also described. Also, the synthesis of the compound, and uses of the compound, such as in a method for detecting the localization of, or identifying, receptors, enzymes or other targets, whether in a cell or in a subject.

摘要翻译： 具有以下结构的化合物：其中R1是H，OH，可光活化部分，荧光部分或放射性部分;其中R2是H，OH，可光活化部分，荧光部分或放射性部分;其中R3是H 或OH;其中R 4是H，OH，可光活化部分，荧光部分或放射性部分; 并且其中R 1，R 2，R 3或R 4中的至少一个是可光活化部分，荧光部分或放射性部分。 还描述了化合物的光学纯对映异构体和盐。 此外，化合物的合成以及化合物的使用，例如在细胞或受试者中检测定位或识别受体，酶或其他靶标的方法中。

公开(公告)号：US07145021B2

公开(公告)日：2006-12-05

申请号：US10401931

申请日：2003-03-28

申请人： Kristian Stromgaard ,  Makiko Suehiro ,  Koji Nakanishi ,  Stine B. Vogensen

发明人： Kristian Stromgaard ,  Makiko Suehiro ,  Koji Nakanishi ,  Stine B. Vogensen

IPC分类号： C07D307/77

CPC分类号： C07D493/20 ,  C07D493/22

摘要： The subject invention provides compounds having the structure: wherein R1 is H, OH, a photoactivatable moiety, a fluorescent moiety, or a radioactive moiety; R2 is H, OH, a photoactivatable moiety, a fluorescent-moiety, or a radioactive moiety; R3 is H or OH; R4 is H, OH, a photoactivatable moiety, a fluorescent moiety, or a radioactive moiety; and wherein at least one of R1, R2, R3, or R4 is a photoactivatable moiety, a fluorescent moiety, or a radioactive moiety, or an optically pure enantiomer of the compound or wherein R1 is H or OH; R2 is H, OH, halogen, unsubstituted or substituted, straight or branched (C1–C5) alkyl group, (C2–C5) alkenyl, or a (C2–C5) alkynyl, (C1–C5) alkoxy, (C2–C5) alkenyloxy, or (C2–C5) alkynyloxy, —N3, —COR5, —CONR5R6, —CO2R5, —OCOR5, —NH(OH), —NR5R6, —NHCOR5, —N(OH)COR5, —CH2OR5, —OCH2CO2R5, —CH2SR5, —CH2NR5R6, —SR5, —OSR5, or —NR5SO2R6, where R5 and R6 are each independently hydrogen, substituted or unsubstituted (C1–C5) alkyl, (C2–C5) alkenyl, or (C2–C5) alkynyl, or a cycloalkyl or aryl group having 3 to 10 carbon atoms; R3 is H or OH; R4 is H, (C1–C10) alkyl, (C1–C10) alkenyl, (C1–C10) alkynyl, -A-Ar, -A-Z-Ar, —SO2—Ar, or -A-NR5, or —R7, where A, Z and Ar are as defined herein, and the use of the compounds for detecting or identifying a receptor which binds the compounds of the invention or for treating a PAF associated condition in a subject.

公开(公告)号：US20050119336A1

公开(公告)日：2005-06-02

申请号：US10925209

申请日：2004-08-24

申请人： Koji Nakanishi ,  Stanislav Jaracz ,  Kristian Stromgaard

发明人： Koji Nakanishi ,  Stanislav Jaracz ,  Kristian Stromgaard

IPC分类号： A61K31/365 ,  C07D20060101 ,  C07D307/93 ,  C07D307/94 ,  C07D311/94 ,  C07D311/96 ,  C07D493/14

CPC分类号： C07D493/22

摘要： The subject invention provides ginkgolide C derivatives compounds having the structure: wherein R is H or -A-Ar, where A is an alkyl group; and Ar is an aryl group, which may contain heteroatoms and may be unsubstituted or substituted by one to five substituents each selected from the group consisting of hydrogen, alkoxy, —CH2CO2R4, and —CH2CONR5R6; where R4 is an alkyl group; and R5 and R6 are each, independently, hydrogen or a branched or unbranched alkyl group; wherein R1 is H or —COR7, where R7 is alkyl, aryl or amino; wherein R2 is present or absent, and when present is H, —COR8 or —CO-Z-R8; where R8 is alkyl, aryl or amino; and Z is oxygen; wherein R3 is present or absent, and when present is —COR9; where R9 is alkyl or aryl; wherein only one of R2 or R3 is present in the compound; wherein only two of R, R1, R2 and R3 are H; and wherein each of a and b designates a single covalent bond which is present or absent, where bond a is present when R3 is absent and bond b is present when R2 is absent; or an optically pure enantiomer of the compound. Additionally, the subject invention provides methods of inhibiting the activity of a glycine receptor using these compounds.

摘要翻译： 本发明提供具有以下结构的银杏内酯C衍生物化合物：其中R是H或-A-Ar，其中A是烷基; 并且Ar是可以含有杂原子的芳基，并且可以是未取代的或被一至五个选自氢，烷氧基，-CH 2 CO 2， R 4，R 4，R 4，R 6， 其中R 4是烷基; 和R 5和R 6各自独立地为氢或支链或非支链烷基; 其中R 1是H或-COR 7，其中R 7是烷基，芳基或氨基; 其中R 2存在或不存在，并且当存在时为H，-COR 8或-CO-Z-R 8; 其中R 8是烷基，芳基或氨基; Z为氧; 其中R 3存在或不存在，并且当存在时为-COR 9; 其中R 9是烷基或芳基; 其中R 2和R 3中只有一个存在于化合物中; 其中R 1，R 2，R 2和R 3中只有两个是H; 并且其中a和b中的每一个表示存在或不存在的单个共价键，其中当R 3不存在时存在键a，并且当R 2' 缺席; 或该化合物的光学纯对映异构体。 此外，本发明提供了使用这些化合物抑制甘氨酸受体的活性的方法。

公开(公告)号：US07429670B2

公开(公告)日：2008-09-30

申请号：US10925209

申请日：2004-08-24

申请人： Koji Nakanishi ,  Stanislav Jaracz ,  Kristian Stromgaard

发明人： Koji Nakanishi ,  Stanislav Jaracz ,  Kristian Stromgaard

IPC分类号： C07D305/14 ,  A01K43/12

CPC分类号： C07D493/22

摘要： The subject invention provides ginkgolide C derivatives compounds having the structure: wherein R is H or -A-Ar, where A is an alkyl group; and Ar is an aryl group, which may contain heteroatoms and may be unsubstituted or substituted by one to five substituents each selected from the group consisting of hydrogen, alkoxy, —CH2CO2R4, and —CH2CONR5R6; where R4 is an alkyl group; and R5 and R6 are each, independently, hydrogen or a branched or unbranched alkyl group; wherein R1 is H or —COR7, where R7 is alkyl, aryl or amino; wherein R2 is present or absent, and when present is H, —COR8 or —CO—Z—R8; where R8 is alkyl, aryl or amino; and Z is oxygen; wherein R3 is present or absent, and when present is —COR9; where R9 is alkyl or aryl; wherein only one of R2 or R3 is present in the compound; wherein only two of R, R1, R2 and R3 are H; and wherein each of a and b designates a single covalent bond which is present or absent, where bond a is present when R3 is absent and bond b is present when R2 is absent; or an optically pure enantiomer of the compound. Additionally, the subject invention provides methods of inhibiting the activity of a glycine receptor using these compounds.

摘要翻译： 本发明提供具有以下结构的银杏内酯C衍生物化合物：其中R是H或-A-Ar，其中A是烷基; 并且Ar是可以含有杂原子的芳基，并且可以是未取代的或被一至五个选自氢，烷氧基，-CH 2 CO 2， R 4，R 4，R 4，R 6， 其中R 4是烷基; 和R 5和R 6各自独立地为氢或支链或非支链烷基; 其中R 1是H或-COR 7，其中R 7是烷基，芳基或氨基; 其中R 2存在或不存在，并且当存在时为H，-COR 8或-CO-Z-R 8; 其中R 8是烷基，芳基或氨基; Z为氧; 其中R 3存在或不存在，并且当存在时为-COR 9; 其中R 9是烷基或芳基; 其中R 2和R 3中只有一个存在于化合物中; 其中R 1，R 2，R 2和R 3中只有两个是H; 并且其中a和b中的每一个表示存在或不存在的单个共价键，其中当R 3不存在时存在键a，并且当R 2' 缺席; 或该化合物的光学纯对映异构体。 此外，本发明提供了使用这些化合物抑制甘氨酸受体的活性的方法。

公开(公告)号：US09139615B2

公开(公告)日：2015-09-22

申请号：US14116862

申请日：2012-05-11

申请人： Anders Bach ,  Kristian Stromgaard

发明人： Anders Bach ,  Kristian Stromgaard

IPC分类号： C07K7/06

CPC分类号： C07K7/06

摘要： The invention provides novel potent inhibitors of the ternary protein complex of nNOS, PSD-95, and the NMDA receptor and pharmaceutical compositions comprising the inhibitors for prophylaxis and/or treatment of excitotoxic-related disease and chronic pain conditions in a subject. The inhibitors are dimeric PSD-95 inhibitors comprising a first peptide or peptide analogue linked to a second peptide or peptide analogue by a linker, wherein the first and the second peptide or peptide analogue comprise at least four amide-bonded residues having a sequence YTXV (SEQ ID NO: 5) or YSXV (SEQ ID NO: 6), wherein a. Y is selected from among E, Q, and A, or an analogue thereof, and b. X is selected from among A, Q, D, N, N-Me-A, N-Me-Q, N-Me-D, and N-Me-N or an analogue thereof, and wherein a Cell Penetrating Peptide (CPP) is linked to the linker or to an amino acid side chain of the first and second peptide or peptide analogue. The linker can be a PEG or NPEG linker.

摘要翻译： 本发明提供了nNOS，PSD-95和NMDA受体的三元蛋白复合物的新型有效抑制剂和包含用于预防和/或治疗受试者兴奋性毒性相关疾病和慢性疼痛病症的抑制剂的药物组合物。 抑制剂是包含通过接头与第二肽或肽类似物连接的第一肽或肽类似物的二聚PSD-95抑制剂，其中第一和第二肽或肽类似物包含至少四个具有序列YTXV（与 SEQ ID NO：5）或YSXV（SEQ ID NO：6），其中a。 Y选自E，Q和A，或其类似物，b。 X选自A，Q，D，N，N-Me-A，N-Me-Q，N-Me-D和N-Me-N或其类似物，其中细胞穿透肽 ）与第一和第二肽或肽类似物的接头或氨基酸侧链连接。 接头可以是PEG或NPEG接头。

公开(公告)号：US09241967B2

公开(公告)日：2016-01-26

申请号：US13002638

申请日：2009-07-09

申请人： Anders Bach ,  Kristian Stromgaard

发明人： Anders Bach ,  Kristian Stromgaard

IPC分类号： A61K38/08 ,  C07K7/06 ,  C12N5/071 ,  A61P25/00 ,  A61K38/07 ,  A61K47/48 ,  C07K5/103 ,  C07K5/113 ,  C07K14/705

CPC分类号： C07K7/06 ,  A61K38/00 ,  A61K38/07 ,  A61K38/08 ,  A61K47/64 ,  C07K5/1008 ,  C07K5/1013 ,  C07K5/1021 ,  C07K14/70571

摘要： The present invention is directed to the provision of small molecule inhibitors of the PSD-95/NMDA receptor interaction, employing an undecapeptide corresponding to the C-terminal of the NMDA as a template for finding lead candidates. A compound (NMDAR/PSD-95 inhibitor) of the invention includes a peptide or peptide analogue comprising at least four peptide bonded residues having the sequence YTXV or YSXV, wherein Y is selected from among E, Q, and A, or an analogue thereof and X is selected from among A, Q, D, N, N-Me-A, N-Me-Q, N-Me-D, and N-Me-N or an analogue thereof, wherein an amino-terminal residue of the peptide is N-alkylated. Alternatively the compound of the invention comprises a first peptide or peptide analogue linked to a second peptide or peptide analogue by a linker, where the first and second peptide or peptide analogue each comprise at least four peptide bonded residues having the sequence YTXV or YSXV, wherein Y is selected from among E, Q, and A, or an analogue thereof, and X is selected from among A, Q, D, N, N-Me-A, N-Me-Q, N-Me-D, and N-Me-N or an analogue thereof.

摘要翻译： 本发明涉及提供PSD-95 / NMDA受体相互作用的小分子抑制剂，其使用对应于NMDA的C-末端的十一肽作为寻找潜在候选物的模板。 本发明的化合物（NMDAR / PSD-95抑制剂）包括包含至少四个具有序列YTXV或YSXV的肽键残基的肽或肽类似物，其中Y选自E，Q和A，或其类似物 并且X选自A，Q，D，N，N-Me-A，N-Me-Q，N-Me-D和N-Me-N或其类似物，其中氨基末端残基 肽被N-烷基化。 或者，本发明的化合物包含通过接头与第二肽或肽类似物连接的第一肽或肽类似物，其中第一和第二肽或肽类似物各自包含至少四个具有序列YTXV或YSXV的肽键残基，其中 Y选自E，Q和A，或其类似物，X选自A，Q，D，N，N-Me-A，N-Me-Q，N-Me-D和 N-Me-N或其类似物。

公开(公告)号：US20110178022A1

公开(公告)日：2011-07-21

申请号：US13002638

申请日：2009-07-09

申请人： Anders Bach ,  Kristian Stromgaard

发明人： Anders Bach ,  Kristian Stromgaard

IPC分类号： A61K38/08 ,  C07K4/00 ,  C07K7/06 ,  C12N5/071 ,  A61P25/00

CPC分类号： C07K7/06 ,  A61K38/00 ,  A61K38/07 ,  A61K38/08 ,  A61K47/64 ,  C07K5/1008 ,  C07K5/1013 ,  C07K5/1021 ,  C07K14/70571

摘要： The present invention is directed to the provision of small molecule inhibitors of the PSD-95/NMDA receptor interaction, employing an undecapeptide corresponding to the C-terminal of the NMDA as a template for finding lead candidates. A compound (NMDAR/PSD-95 inhibitor) of the invention includes a peptide or peptide analogue comprising at least four peptide bonded residues having the sequence YTXV or YSXV, wherein Y is selected from among E, Q, and A, or an analogue thereof and X is selected from among A, Q, D, N, N-Me-A, N-Me-Q, N-Me-D, and N-Me-N or an analogue thereof, wherein an amino-terminal residue of the peptide is N-alkylated. Alternatively the compound of the invention comprises a first peptide or peptide analogue linked to a second peptide or peptide analogue by a linker, where the first and second peptide or peptide analogue each comprise at least four peptide bonded residues having the sequence YTXV or YSXV, wherein Y is selected from among E, Q, and A, or an analogue thereof, and X is selected from among A, Q, D, N, N-Me-A, N-Me-Q, N-Me-D, and N-Me-N or an analogue thereof.

摘要翻译： 本发明涉及提供PSD-95 / NMDA受体相互作用的小分子抑制剂，其使用对应于NMDA的C-末端的十一肽作为寻找潜在候选物的模板。 本发明的化合物（NMDAR / PSD-95抑制剂）包括包含至少四个具有序列YTXV或YSXV的肽键残基的肽或肽类似物，其中Y选自E，Q和A，或其类似物 并且X选自A，Q，D，N，N-Me-A，N-Me-Q，N-Me-D和N-Me-N或其类似物，其中氨基末端残基 肽被N-烷基化。 或者，本发明的化合物包含通过接头与第二肽或肽类似物连接的第一肽或肽类似物，其中第一和第二肽或肽类似物各自包含至少四个具有序列YTXV或YSXV的肽键残基，其中 Y选自E，Q和A，或其类似物，X选自A，Q，D，N，N-Me-A，N-Me-Q，N-Me-D和 N-Me-N或其类似物。

公开(公告)号：US20140094415A1

公开(公告)日：2014-04-03

申请号：US14116862

申请日：2012-05-11

申请人： Anders Bach ,  Kristian Stromgaard

发明人： Anders Bach ,  Kristian Stromgaard

IPC分类号： C07K7/06

CPC分类号： C07K7/06

摘要： The invention provides novel potent inhibitors of the ternary protein complex of nNOS, PSD-95, and the NMDA receptor and pharmaceutical compositions comprising the inhibitors for prophylaxis and/or treatment of excitotoxic-related disease and chronic pain conditions in a subject. The inhibitors are dimeric PSD-95 inhibitors comprising a first peptide or peptide analogue linked to a second peptide or peptide analogue by a linker, wherein the first and the second peptide or peptide analogue comprise at least four amide-bonded residues having a sequence YTXV or YSXV, wherein a. Y is selected from among E, Q, and A, or an analogue thereof, and b. X is selected from among A, Q, D, N,N-Me-A, N-Me-Q, N-Me-D, and N-Me-N or an analogue thereof, and wherein a Cell Penetrating Peptide (CPP) is linked to the linker or to an amino acid side chain of the first and second peptide or peptide analogue. The linker can be a PEG or NPEG linker.

摘要翻译： 本发明提供了nNOS，PSD-95和NMDA受体的三元蛋白复合物的新型有效抑制剂和包含用于预防和/或治疗受试者兴奋性毒性相关疾病和慢性疼痛病症的抑制剂的药物组合物。 抑制剂是包含通过接头与第二肽或肽类似物连接的第一肽或肽类似物的二聚PSD-95抑制剂，其中第一和第二肽或肽类似物包含至少四个具有序列YTXV的酰胺键合残基或 YSXV，其中a。 Y选自E，Q和A，或其类似物，b。 X选自A，Q，D，N，N-Me-A，N-Me-Q，N-Me-D和N-Me-N或其类似物，其中细胞穿透肽 ）与第一和第二肽或肽类似物的接头或氨基酸侧链连接。 接头可以是PEG或NPEG接头。