JPH04164036A - Antiasthmatic comprising peptide as main agent - Google Patents
Antiasthmatic comprising peptide as main agentInfo
- Publication number
- JPH04164036A JPH04164036A JP2285748A JP28574890A JPH04164036A JP H04164036 A JPH04164036 A JP H04164036A JP 2285748 A JP2285748 A JP 2285748A JP 28574890 A JP28574890 A JP 28574890A JP H04164036 A JPH04164036 A JP H04164036A
- Authority
- JP
- Japan
- Prior art keywords
- amino acid
- acid residues
- positions
- peptide
- sequence
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 24
- 230000001088 anti-asthma Effects 0.000 title claims description 7
- 239000000924 antiasthmatic agent Substances 0.000 title claims description 7
- 239000003795 chemical substances by application Substances 0.000 title abstract 3
- 125000000539 amino acid group Chemical group 0.000 claims abstract description 27
- 230000002209 hydrophobic effect Effects 0.000 claims abstract description 9
- 229940079593 drug Drugs 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- 239000002075 main ingredient Substances 0.000 claims 3
- 230000002889 sympathetic effect Effects 0.000 abstract description 11
- 210000005036 nerve Anatomy 0.000 abstract description 10
- 208000006673 asthma Diseases 0.000 abstract description 9
- 108091000080 Phosphotransferase Proteins 0.000 abstract description 7
- 102000020233 phosphotransferase Human genes 0.000 abstract description 7
- 150000001413 amino acids Chemical group 0.000 abstract description 5
- 230000003834 intracellular effect Effects 0.000 abstract description 4
- 208000030603 inherited susceptibility to asthma Diseases 0.000 abstract description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 abstract 1
- 239000004475 Arginine Substances 0.000 abstract 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 abstract 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 abstract 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 abstract 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 abstract 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 abstract 1
- 239000004472 Lysine Substances 0.000 abstract 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 abstract 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 abstract 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 abstract 1
- 239000004473 Threonine Substances 0.000 abstract 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 abstract 1
- 230000001268 conjugating effect Effects 0.000 abstract 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 abstract 1
- 108090000623 proteins and genes Proteins 0.000 abstract 1
- 102000004169 proteins and genes Human genes 0.000 abstract 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 abstract 1
- 229920001184 polypeptide Polymers 0.000 description 13
- 102000004196 processed proteins & peptides Human genes 0.000 description 13
- 102000030782 GTP binding Human genes 0.000 description 8
- 108091000058 GTP-Binding Proteins 0.000 description 8
- 108091006065 Gs proteins Proteins 0.000 description 8
- 108091006027 G proteins Proteins 0.000 description 6
- 238000006366 phosphorylation reaction Methods 0.000 description 5
- 230000003213 activating effect Effects 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000026731 phosphorylation Effects 0.000 description 4
- 230000004913 activation Effects 0.000 description 3
- 102000030621 adenylate cyclase Human genes 0.000 description 3
- 108060000200 adenylate cyclase Proteins 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 210000002460 smooth muscle Anatomy 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 2
- 229950006790 adenosine phosphate Drugs 0.000 description 2
- -1 atrenaline Chemical compound 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- UDMBCSSLTHHNCD-UHFFFAOYSA-N Coenzym Q(11) Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1O UDMBCSSLTHHNCD-UHFFFAOYSA-N 0.000 description 1
- 239000000150 Sympathomimetic Substances 0.000 description 1
- 210000005091 airway smooth muscle Anatomy 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 229960000265 cromoglicic acid Drugs 0.000 description 1
- IMZMKUWMOSJXDT-UHFFFAOYSA-N cromoglycic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C(O)=O)O2 IMZMKUWMOSJXDT-UHFFFAOYSA-N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229960001361 ipratropium bromide Drugs 0.000 description 1
- KEWHKYJURDBRMN-ZEODDXGYSA-M ipratropium bromide hydrate Chemical compound O.[Br-].O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 KEWHKYJURDBRMN-ZEODDXGYSA-M 0.000 description 1
- 229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 229940127230 sympathomimetic drug Drugs 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は喘息、特に難治性喘息の発作終息に効果のある
抗喘息薬に関するもので、更に詳しくは生体におけるシ
グナル変換蛋白として注目を浴びているＧＴＰ結合蛋白
質の中で、交感神経受容体と共役し、アデニレートシク
ラーゼを活性化することで様々なシグナルのセカンドメ
ツセンジャーであるｃＡＭＰ （サイクリック・アデノ
シン−リン酸）の産生を促進するＧＴＰ結合蛋白質（Ｇ
ｓ）を直接刺激することで、気道平滑筋を弛緩させる作
用を持つ画期的な抗喘息薬に関するものである。[Detailed Description of the Invention] [Field of Industrial Application] The present invention relates to an anti-asthmatic drug that is effective in terminating attacks of asthma, particularly intractable asthma. Among the GTP-binding proteins in the body, it promotes the production of cAMP (cyclic adenosine-phosphate), which is a second messenger for various signals, by coupling with sympathetic nerve receptors and activating adenylate cyclase. GTP-binding protein (G
The present invention relates to an innovative anti-asthmatic drug that has the effect of relaxing airway smooth muscle by directly stimulating s).
気管支平滑筋の交感神経の受容体への刺激は、Ｇｓを活
性化し、ひいてはアゾニレ−トンクラーゼの活性化を促
すことで、細胞内のｃＡＭＰを上昇させる。ｃＡＭＰは
気管支平滑筋の弛緩を促す根本的なメデイエータ−とさ
れ、喘息発作の治療はこのｃＡＭＰを上昇させることに
重きがおかれる。Stimulation of sympathetic nerve receptors in bronchial smooth muscle activates Gs, which in turn promotes activation of azonylate toncrase, thereby increasing intracellular cAMP. cAMP is considered to be a fundamental mediator that promotes relaxation of bronchial smooth muscle, and treatment of asthma attacks focuses on increasing cAMP.
従来の薬剤はテオフィリンに代表されるキサンチン誘導
体、アト°レナリンに代表される交感神経刺激剤、臭化
イプラトロピウムなどの副交感神経遮断剤、クロモグリ
ク酸ナトリウムなどの抗アレルギー剤そしてステロイド
剤であり、受容体刺激の強化や、ｃＡＭＰの分解抑制を
もたらすことで、細胞内ｃＡＭＰ濃度の上昇を促すもの
である。Ｇｓ蛋白の直接活性化によりｃＡＭＰａ度の上
昇を企図されたものはいまだ知られていない。Conventional drugs include xanthine derivatives such as theophylline, sympathomimetic agents such as atrenaline, parasympatholytic agents such as ipratropium bromide, anti-allergic agents such as sodium cromoglycate, and steroids, which act on receptors. It promotes an increase in intracellular cAMP concentration by enhancing stimulation and inhibiting cAMP degradation. There is no known method to increase cAMPa level by directly activating Gs protein.
従来の薬剤では治療し得ないタイプのいわゆる難治性喘
息と呼ばれているものの治療がその主な目的である。難
治性喘息は交感神経の受容体そのものの数の減少やその
Ｇｓへのシグナル伝達機能自体が低下していたりするこ
とがこの原因とされており、結果的には、交感神経受容
体を介して、Ｇｓ蛋白を刺激する従来の薬剤では、アデ
ニレートシクラーゼの活性化を惹起することができず、
気管支平滑筋の弛緩を促すｃＡＭＰの濃度を上昇させ得
ない。交感神経の受容体に代わって直接Ｇｓを刺激する
ことができれば、この問題は解決可能と思われる。Its main purpose is to treat so-called intractable asthma, a type of asthma that cannot be treated with conventional drugs. Intractable asthma is thought to be caused by a decrease in the number of sympathetic nerve receptors and a decline in their signal transmission function to Gs, and as a result, , conventional drugs that stimulate Gs protein cannot induce activation of adenylate cyclase,
It cannot increase the concentration of cAMP, which promotes relaxation of bronchial smooth muscle. This problem seems to be solvable if Gs can be directly stimulated instead of the sympathetic receptors.
本件出願人は永年にわたる研究の成果から、Ｇｓと共役
する交感神経受容体の細胞内ドメインを同定し、このド
メインと相同のアミノ酸配列をもったポリペプチドがＧ
ＴＰ結合蛋白質と共役することを発見した。さらには、
このポリペプチドは、細胞膜環境においてアデニレート
シクラーゼを活性化させ、ｃ Ａ Ｍ Ｐの上昇を促す
ことも見いだしている。Based on the results of many years of research, the applicant has identified an intracellular domain of a sympathetic nerve receptor that couples with Gs, and has identified a polypeptide with an amino acid sequence homologous to this domain.
It was discovered that it binds to TP-binding protein. Furthermore,
This polypeptide has also been found to activate adenylate cyclase in the cell membrane environment, promoting an increase in c AMP.
本発明は、上記のポリペプチドを薬剤として用いること
により、Ｇｓ蛋白への刺激伝達が低下している難治性喘
息にも交感神経受容体を介さず、Ｇｓ蛋白を直接刺激す
ることを可能としたものである。The present invention has made it possible to directly stimulate the Gs protein without going through sympathetic nerve receptors, even in cases of refractory asthma in which stimulus transmission to the Gs protein is reduced, by using the above-mentioned polypeptide as a drug. It is something.
本発明における基本構造ｒＲＲ５ＳＫＦＣＬＫＥＨＫＡ
ＬＫＪからなるポリペプチドは、生体内に存在する交感
神経受容体の一部、特にＧｓ蛋白と結合する部分を組成
するアミノ酸と一次配列が同一である。従って、このポ
リペプチドは、本来的にＧｓ蛋白と直接結合し、活性化
する作用をもち、その活性化能は、従来知られているい
かなる薬剤よりも強力である。Basic structure rRR5SKFCLKEHKA in the present invention
The polypeptide consisting of LKJ has the same primary sequence as the amino acids that make up a part of the sympathetic nerve receptor existing in the body, especially the part that binds to Gs protein. Therefore, this polypeptide inherently has the effect of directly binding and activating the Gs protein, and its activating ability is stronger than any conventionally known drug.
一方、ペプチドに含まれる２種の残基、セリン残基Ｓと
スレオニン残基Ｔ１そしてチロシン残基Ｙは、生体内に
存在するキナーゼにより、リン酸化を受けることが知ら
れている代表的なアミノ酸残基であり、生体内では受容
体のキナーゼによるリン酸化は受容体とＧｓ蛋白の共役
を阻害する方向に働いているとされる。つまり、基本構
成配列第３位、第４位の位置にあるアミノ酸残基を抗リ
ン酸化性のアミノ酸残基に変異することにより、キナー
ゼによるリン酸化を防止することができ、ポリペプチド
のＧ蛋白活性化能はキナーゼにより不活化されることが
ないまた、このポリペプチドは、疎水性度が低く疎水性
度の高い細胞膜を通過することができないので細胞内に
入ることができず、細胞外から細胞内にあるＧ蛋白の刺
激しか出来ないという問題をふくんでいる。On the other hand, two types of residues contained in the peptide, serine residue S, threonine residue T1, and tyrosine residue Y, are representative amino acids known to be phosphorylated by kinases present in living organisms. In vivo, phosphorylation of receptors by kinases is thought to work in the direction of inhibiting the coupling between receptors and Gs proteins. In other words, by mutating the amino acid residues in the 3rd and 4th positions of the basic constituent sequence to anti-phosphorylation amino acid residues, phosphorylation by kinases can be prevented, and the G protein of the polypeptide can be prevented from being phosphorylated. The activation ability cannot be inactivated by kinases. In addition, this polypeptide has low hydrophobicity and cannot pass through the highly hydrophobic cell membrane, so it cannot enter the cell and cannot be accessed from outside the cell. This includes the problem that it can only stimulate G proteins within cells.
そこで、上記の基本構成配列を例にとり第１０位の位置
にあるアミノ酸残基を疎水性のアミノ酸残基に置換する
ことにより、ポリペプチドの疎水性度を上げ、細胞膜を
通過して直接Ｇ蛋白の刺激することを可能にすることが
できる。Therefore, taking the above basic constituent sequence as an example, by substituting the amino acid residue at position 10 with a hydrophobic amino acid residue, the degree of hydrophobicity of the polypeptide is increased, allowing it to pass through the cell membrane and directly form a G protein. can be made possible to stimulate.
またＧｓを刺激するためにはＮ端の第１位と第２位及び
Ｃ端の最後位と最後から３番目もしくは４番目の位置に
、Ｒ，に、Ｈのいずれかの塩基性アミノ酸残基を配置す
ることが必須であると考えられる。In addition, in order to stimulate Gs, add basic amino acid residues such as R, H, or H to the 1st and 2nd positions of the N-terminus and the last and 3rd or 4th positions of the C-terminus. It is considered essential to place a
このためこの必須な配列の順序をくずさず、目的に見合
うポリペプチドを合成しなくてはならない。Therefore, it is necessary to synthesize a polypeptide that meets the purpose without disturbing the order of this essential sequence.
以下、図表により本発明の詳細な説明する。 Hereinafter, the present invention will be explained in detail with reference to figures and tables.
第１表は配列の基本的変化を示すもので、ｌは基本構成
配列、２はＮ端の第１位と第２位及びＣ端の最後位と最
後から３番目もしくは４番目の位置に、Ｒ，に、Ｈのい
ずれかの塩基性アミノ酸残基を配置する配列の条件を満
たした配列の例、３は上記基本配列条件位置以外の位置
に配列されるアミノ酸残基をキナーゼによって最もリン
酸化され易いＳ、Ｔ、Ｙの各残基以外のアミノ酸残基と
した配列の例である。Table 1 shows the basic changes in the arrangement, where l is the basic constituent arrangement, 2 is the first and second positions at the N end, and the last and third or fourth positions from the end at the C end. An example of a sequence that satisfies the sequence conditions in which one of the basic amino acid residues of H is placed in R and H. 3 is an example of a sequence that satisfies the sequence condition in which one of the basic amino acid residues of H is placed in R, 3. This is an example of a sequence in which amino acid residues other than the S, T, and Y residues that are easily affected are used.
４は上記基本配列条件位置以外の位置に配列されるアミ
ノ酸残基を、塩基性あるいは疎水性のアミノ酸残基とし
た配列の例である。4 is an example of a sequence in which the amino acid residues arranged at positions other than the above basic sequence condition positions are basic or hydrophobic amino acid residues.
５は上記基本配列条件位置以外の位置に配列されるアミ
ノ酸残基を、全て疎水性のアミノ酸残基とした配列の例
である。No. 5 is an example of a sequence in which all amino acid residues arranged at positions other than the above basic sequence condition positions are hydrophobic amino acid residues.
交感神経受容体の減少や損傷がなく、生体内にキナーゼ
の影響のない場合には、ｌの基本構成配列によるポリペ
プチドあるいは２のポリペプチドを用いることによりＧ
蛋白の刺激がおこなわれる。If there is no decrease or damage to sympathetic nerve receptors and no effect of kinase in vivo, G
Protein stimulation takes place.
生体内にキナーゼの影響が強く、ポリペプチドのリン酸
化が危惧される場合には、３の置換例によるポリペプチ
ドを用いることにより、ペプチドのリン酸化を防止し、
Ｇ蛋白との定着を容易にして共役を助長する。更に、４
あるいは５に示すのは交感神経受容体に減少や損傷が認
められる場合にポリペプチドの中で疎水性のアミノ酸残
基を多く含むものを用いることにより、ペプチドが細胞
膜を通過し、直接Ｇ蛋白に働きかけられるようにする置
換例の一部である。If there is a strong influence of kinases in vivo and there is a risk of phosphorylation of the polypeptide, use the polypeptide according to substitution example 3 to prevent phosphorylation of the peptide,
It facilitates fixation with G protein and promotes conjugation. Furthermore, 4
Alternatively, as shown in 5, when sympathetic nerve receptors are decreased or damaged, by using a polypeptide containing many hydrophobic amino acid residues, the peptide can pass through the cell membrane and directly connect to G protein. These are some examples of substitutions that can be made to work.
第１表に示した配列例は、安定性のある代表的なもので
あるが、それ以外の置換例によっても良いことは勿論で
ある。Although the arrangement examples shown in Table 1 are typical and stable ones, it goes without saying that other substitution examples may also be used.
第２表は、本発明によるポリペプチドの構成に用いるこ
との出来るアミノ酸残基を、性質別に分類例示したもの
で、これらのアミノ酸残基を用いて病状に応じた置換を
行い、活用することが可能である。Table 2 lists examples of amino acid residues that can be used to construct the polypeptide according to the present invention, categorized by property. It is possible.
本発明は以上のように構成したので、Ｇｓ蛋白への直接
的な働きかけを可能にし、これまで困難であった難治性
気管支喘息の治療に画期的な進歩をもたらすもので、極
めて有効な発明といえる。The present invention, constructed as described above, enables direct action on the Gs protein and brings about revolutionary progress in the treatment of intractable bronchial asthma, which has been difficult until now.It is an extremely effective invention. It can be said.
第１表は、本発明による薬物の一次配列を示す配列表、
第２表は、略号の名称を示す略語表である。Table 1 is a sequence listing showing the primary sequence of the drug according to the present invention;
Table 2 is an abbreviation table showing the names of abbreviations.
Claims (4)
配列からなり、Ｎ端の第１位と第２位及びＣ端の最後位
と最後から３番目もしくは４番目の位置に、Ｒ、Ｋ、Ｈ
のいずれかの塩基性アミノ酸残基を配置して成るペプチ
ドを主剤とする抗喘息薬(1) It consists of a sequence of 6 to 50 amino acid residues as a whole, and R, K,H
An anti-asthmatic drug whose main ingredient is a peptide consisting of any of the following basic amino acid residues:
ら３番目もしくは４番目の位置以外の位置に配列される
アミノ酸残基は、Ｓ、Ｔ、Ｙ以外のアミノ酸残基を適宜
に配置してなる特許請求の範囲（１）記載のペプチドを
主剤とする抗喘息薬(2) Amino acid residues arranged at positions other than the 1st and 2nd positions at the N-terminus and the last and 3rd or 4th positions at the C-terminus are amino acid residues other than S, T, and Y. An anti-asthmatic drug whose main ingredient is the peptide according to claim (1), which has groups appropriately arranged.
ら３番目もしくは４番目の位置以外の位置に配列される
アミノ酸残基は塩基性アミノ酸残基と疎水性アミノ酸残
基を適宜に配置してなる特許請求の範囲（１）記載のペ
プチドを主剤とする抗喘息薬(3) Amino acid residues arranged at positions other than the 1st and 2nd positions at the N-terminus and the last and 3rd or 4th positions at the C-terminus are basic amino acid residues and hydrophobic amino acid residues. An anti-asthmatic drug based on the peptide according to claim (1), which has groups appropriately arranged.
ら３番目もしくは４番目の位置以外の位置に配列される
アミノ酸残基は全て疎水性アミノ酸残基を適宜に配置し
てなる特許請求の範囲（１）記載のペプチドを主剤とす
る抗喘息薬(4) All amino acid residues arranged at positions other than the 1st and 2nd positions at the N-terminus and the last, 3rd or 4th positions at the C-terminus are all hydrophobic amino acid residues arranged as appropriate. An anti-asthmatic drug containing as a main ingredient the peptide according to claim (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2285748A JPH04164036A (en) | 1990-10-25 | 1990-10-25 | Antiasthmatic comprising peptide as main agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2285748A JPH04164036A (en) | 1990-10-25 | 1990-10-25 | Antiasthmatic comprising peptide as main agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH04164036A true JPH04164036A (en) | 1992-06-09 |
Family
ID=17695542
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2285748A Pending JPH04164036A (en) | 1990-10-25 | 1990-10-25 | Antiasthmatic comprising peptide as main agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH04164036A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003530875A (en) * | 2000-04-21 | 2003-10-21 | ニュー イングランド メディカル センター ホスピタル インコーポレイテッド | Agonists and antagonists of G protein-coupled receptors (GPCRs) and methods of using them to activate and inhibit GPCRs |
| US8324172B2 (en) | 2000-04-21 | 2012-12-04 | Tufts Medical Center, Inc. | G protein coupled receptor agonists and antagonists and methods of activating and inhibiting G protein coupled receptors using the same |
-
1990
- 1990-10-25 JP JP2285748A patent/JPH04164036A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003530875A (en) * | 2000-04-21 | 2003-10-21 | ニュー イングランド メディカル センター ホスピタル インコーポレイテッド | Agonists and antagonists of G protein-coupled receptors (GPCRs) and methods of using them to activate and inhibit GPCRs |
| US8324172B2 (en) | 2000-04-21 | 2012-12-04 | Tufts Medical Center, Inc. | G protein coupled receptor agonists and antagonists and methods of activating and inhibiting G protein coupled receptors using the same |
| US8563519B2 (en) | 2000-04-21 | 2013-10-22 | Tufts Medical Center, Inc. | Methods of activating or inhibiting G protein coupled receptors (GPCRs) |
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