JPS62277398A - Polypeptide compound - Google Patents
Polypeptide compoundInfo
- Publication number
- JPS62277398A JPS62277398A JP61173457A JP17345786A JPS62277398A JP S62277398 A JPS62277398 A JP S62277398A JP 61173457 A JP61173457 A JP 61173457A JP 17345786 A JP17345786 A JP 17345786A JP S62277398 A JPS62277398 A JP S62277398A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- alanine
- formula
- extracted
- under reduced
- 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.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 41
- 108090000765 processed proteins & peptides Proteins 0.000 title claims description 8
- 229920001184 polypeptide Polymers 0.000 title claims description 4
- 102000004196 processed proteins & peptides Human genes 0.000 title claims description 4
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical group NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000000126 substance Substances 0.000 claims abstract description 8
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical group CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims abstract description 6
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical group CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims abstract description 6
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical group C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims abstract description 6
- 229960000310 isoleucine Drugs 0.000 claims abstract description 6
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Chemical group CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims abstract description 6
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical group CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims abstract description 5
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Chemical group CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims abstract description 5
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Chemical group CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000004473 Threonine Chemical group 0.000 claims abstract description 5
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical group CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229940000635 beta-alanine Drugs 0.000 claims abstract description 5
- 239000004474 valine Chemical group 0.000 claims abstract description 5
- 235000004279 alanine Nutrition 0.000 claims abstract description 4
- AGPKZVBTJJNPAG-UHNVWZDZSA-N L-allo-Isoleucine Chemical group CC[C@@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-UHNVWZDZSA-N 0.000 claims abstract 2
- 229940024606 amino acid Drugs 0.000 claims description 3
- 235000001014 amino acid Nutrition 0.000 claims description 3
- 150000001413 amino acids Chemical class 0.000 claims description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 abstract description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 abstract description 3
- 238000006243 chemical reaction Methods 0.000 abstract description 3
- 239000000741 silica gel Substances 0.000 abstract description 3
- 229910002027 silica gel Inorganic materials 0.000 abstract description 3
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 2
- 239000002904 solvent Substances 0.000 abstract description 2
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 abstract 2
- 239000007788 liquid Substances 0.000 abstract 2
- 238000004128 high performance liquid chromatography Methods 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 12
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 8
- 238000001819 mass spectrum Methods 0.000 description 8
- 238000000862 absorption spectrum Methods 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 238000001228 spectrum Methods 0.000 description 6
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 5
- 230000014759 maintenance of location Effects 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- KSPIYJQBLVDRRI-UHFFFAOYSA-N N-methylisoleucine Chemical compound CCC(C)C(NC)C(O)=O KSPIYJQBLVDRRI-UHFFFAOYSA-N 0.000 description 4
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- GDFAOVXKHJXLEI-VKHMYHEASA-N N-methyl-L-alanine Chemical compound C[NH2+][C@@H](C)C([O-])=O GDFAOVXKHJXLEI-VKHMYHEASA-N 0.000 description 3
- AKCRVYNORCOYQT-YFKPBYRVSA-N N-methyl-L-valine Chemical compound CN[C@@H](C(C)C)C(O)=O AKCRVYNORCOYQT-YFKPBYRVSA-N 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000006911 enzymatic reaction Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- KSPIYJQBLVDRRI-RITPCOANSA-N (2S,3R)-3-methyl-2-(methylamino)pentanoic acid Chemical compound CC[C@@H](C)[C@H]([NH2+]C)C([O-])=O KSPIYJQBLVDRRI-RITPCOANSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 108010074725 Alpha,alpha-trehalose phosphorylase Proteins 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- -1 arrowisoleucine Chemical compound 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000002021 butanolic extract Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- XJODGRWDFZVTKW-ZCFIWIBFSA-N n-methylleucine Chemical compound CN[C@@H](C(O)=O)CC(C)C XJODGRWDFZVTKW-ZCFIWIBFSA-N 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 210000002700 urine Anatomy 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） 本発明は新規なポリペプチド化合物に関する。[Detailed description of the invention] (Industrial application field) The present invention relates to novel polypeptide compounds.
（発明の構成）
本発明者等は各種の海産動物体内に含まれる生理活性物
質を探索中のところ、海綿中に存在するある種の物質が
、酵素阻害作用を有することを確認し本発明を達成した
。(Structure of the Invention) While searching for physiologically active substances contained in the bodies of various marine animals, the present inventors confirmed that certain substances present in sponges have an enzyme-inhibiting effect. Achieved.
本発明の詳細な説明するに、本発明における前示（１）
式の化合物は文献未載の新規化合物であって、例えば後
記実施例に示すように、ある鵠の海綿（肋あ■江ムｓｐ
、）を破砕してホモジナイズし適当な溶媒を用いて抽出
処理し、カラムクロマトグラフィーにより精製すること
によって単離することができる。For detailed explanation of the present invention, the foregoing (1) of the present invention
The compound of the formula is a new compound that has not been described in any literature, and for example, as shown in the Examples below, it is
, ), homogenization, extraction using an appropriate solvent, and purification by column chromatography.
本発明の化合物としては、例えば、前示（＋）式におけ
るＸとして、アラニン（Ａｌａ）、β−アラニン（β−
Ａｌａ）、Ｎ−メチルアラニン（Ｎ−Ｍｅ−Ａｌａ）、
トレオニン（Ｔｈｒ）、ロイシン（Ｌｅｕ）、バリン（
Ｖａｔ）、Ｎ−メチルバリン（Ｎ−Ｍｅ−Ｖａｌ）、イ
ソロイシン（ｌｌｅ）、７０イソロイシン（ａ ｌ Ｉ
ｏ−ｌ １ｅ）、Ｎ−メチルイソロイシン（Ｎ−Ｍｅ−
Ｉ Ｉｅ）、Ｎ−メチルアロイソロイシン（Ｎ−Ｍｅ−
ａｌ ｌｏ−ｌ Ｉｅ）等のアミノ酸から構成される種
々のべブチド鎖である物質が挙げられる。Examples of the compounds of the present invention include alanine (Ala), β-alanine (β-
Ala), N-methylalanine (N-Me-Ala),
Threonine (Thr), Leucine (Leu), Valine (
Vat), N-methylvaline (N-Me-Val), isoleucine (lle), 70 isoleucine (al I
o-l 1e), N-methylisoleucine (N-Me-
I Ie), N-methylalloisoleucine (N-Me-
Examples include substances that are various bebutide chains composed of amino acids such as al lo-l Ie).
具体的には例えば、前示（１）式におけるＲが（Ａ）で
あって、Ｘが次のペプチド鎖、
−（β−Ａｌａ）−（Ｌｅｕ）−（Ｎ−Ｍｅ−１１ｅｌ
（β−Ａｌ ａ ） −（ＬＬＬＱ −＋ ＋ｅ）−（
Ｎ−Ｍｅ−ｖａ＋）−（Ｎ−Ｍｅ−Ａｌａ）−（β−Ａ
ｌａ）−（Ｌｅｕ）−（Ｎ−Ｍｅ−Ｌｂ−ｌ １ｅ）−
で示されるポリペプチド化合物［後記化合物（ロ）］、
前示（＋）式におけるＲが（８）であって、Ｘ及びＹが
夫々次のペプチド鎖、
Ｘニー（β−Ａｌａ）−（Ｌｅｕ）−（Ｎ−Ｍｅ−１ｔ
ｅｌ（β−Ａ ｌ ａ ） −（ＬＬＬＱ −Ｉｌｅ）
−
Ｙ：Ｈ−（Ｎ−Ｍｅ−Ａｌａ）−（β−Ａｌａ）−（Ｌ
ｅｕ）−（Ｎ−Ｍｅ−Ｊｌｇ−ｌ １ｅ）で示されるポ
リペプチド化合物［後記化合物（ニ）コ 、
前示（＋）式において、Ｒが（８）式であって、Ｘ及び
Ｙが夫々次のペプチド鎖、
Ｘニー（β−Ａｌａ）−（Ｌｅｕｌ
ｙ：ｏ−（Ｎ−Ｍｅ−Ａｌａ）−（β−Ａｌａ）−（Ｌ
ｅｕ）−（Ｎ−Ｍｅ−ａｌ Ｉｏ−Ｉ Ｉｅ）て示され
るポリペプチド化合物［後記化合物（ホ）］等が挙げら
れる。Specifically, for example, R in the above formula (1) is (A), and X is the following peptide chain, -(β-Ala)-(Leu)-(N-Me-11el
(β-Ala) −(LLLQ −+ +e) −(
N-Me-va+)-(N-Me-Ala)-(β-A
la)-(Leu)-(N-Me-Lb-l 1e)- [compound (b) below], R in the above formula (+) is (8), and X and Y is respectively the following peptide chain,
el(β-Ala)-(LLLQ-Ile)
- Y:H-(N-Me-Ala)-(β-Ala)-(L
A polypeptide compound represented by eu)-(N-Me-Jlg-l 1e) [Compound (d)co described below, in the above formula (+), R is the formula (8), and X and Y are each The following peptide chain,
eu)-(N-Me-al Io-I Ie) [compound (e) described below], and the like.
本発明の化合物の構造は、比旋光度、ＵＶ吸収スペクト
ル、ＩＲ吸収スペクトル、マススペクトル（ＦＡ８ＭＳ
）、ＩＨＮＭＲ及び＋３ｃ ＮＭＲ等の測定結果から確
認された。The structure of the compound of the present invention can be determined by specific rotation, UV absorption spectrum, IR absorption spectrum, mass spectrum (FA8MS
), IHNMR, +3c NMR, and other measurement results.
（発明の効果）
本発明における前示（１）式の化合物は、優れた酵素反
応阻害活性を有し、しかも毒性が低いので、生化学用試
薬剤としての用途が期待される。(Effects of the Invention) The compound of formula (1) of the present invention has excellent enzyme reaction inhibiting activity and low toxicity, and is therefore expected to be used as a biochemical reagent.
（実施例） 以下本発明を実施例について更に詳細に説明する。(Example) The present invention will be described in more detail below with reference to Examples.
実施例
沖縄慶良問列島海域で採取した海綿（１…田山ｉ９ｐ、
）海綿５００ ｇ （湿重量）を破砕してホモジナイズ
し、Ｔｏ ！エタノール１０００ ｍｌを用いて室温で
３回抽出処理し、抽出液を合して減圧上濃縮し乾固した
。残渣を１５０１の水に懸濁して、ｎ−ブタノール１５
０１を加えて３回抽出処理し、得られたｎ−ブタノール
抽出液に水を加えて減圧下濃縮乾固して抽出物９．２ｇ
を採取した。Example: Sponges collected in the sea area of Keratoi Islands, Okinawa (1...Tayama i9p,
) 500 g (wet weight) of sponge was crushed and homogenized, and To! Extraction was performed three times at room temperature using 1000 ml of ethanol, and the extracts were combined and concentrated under reduced pressure to dryness. The residue was suspended in 150 ml of water and 15 ml of n-butanol was added.
01 was added and extracted three times, water was added to the obtained n-butanol extract, and the mixture was concentrated to dryness under reduced pressure to obtain 9.2 g of extract.
was collected.
この抽出物をシリカゲル（メルク社ｉ！Ａｒｔ７７３４
）３０ ｇにメタノールを用いて吸着させ、メタノール
を減圧下除去した後シリカゲルカラム（４５０ｇ）にの
せ、２７００ ｍｌのクロロホルム、２７００ ｍｌの
クロロホルム−メタノール（９：Ｉ）、２７００ ｍｌ
のクロロホルム−メタノール（８：２）及び２７００
ｍｌのクロロホルム−メタノール（１：Ｉ）を用いて順
次溶出した。This extract was added to silica gel (Merck i! Art 7734).
) was adsorbed using methanol, and after removing methanol under reduced pressure, it was placed on a silica gel column (450 g), and 2700 ml of chloroform, 2700 ml of chloroform-methanol (9:I), and 2700 ml were added.
of chloroform-methanol (8:2) and 2700
Elution was performed sequentially using 1:1 ml of chloroform-methanol.
５４００ ｉｆから７２００ ｍｌの溶出画分を採取し
、濃縮乾固し、得られた１８５０ ｍｇの残渣を活性ア
ルミナ（和光純薬社製２００メツシュ）５０ｇを充填し
たカラムにかけ、２７００ ｎｉｌのクロロホルム−メ
タノール（９５：５）を用いて溶出し、２０１から５０
１の両分を集め、濃縮乾固して白色粉末１．７５ ｇ
（粗製物という）を得た。7200 ml of elution fraction was collected from 5400 if, concentrated to dryness, and the resulting 1850 mg residue was applied to a column packed with 50 g of activated alumina (200 mesh manufactured by Wako Pure Chemical Industries, Ltd.), and 2700 nil chloroform-methanol was added. (95:5), elute from 201 to 50
Collect both parts of 1 and concentrate to dryness to obtain 1.75 g of white powder.
(referred to as crude product) was obtained.
この白色粉末２７４ ｍｇを、ＯＤＳカラム（野村化学
製Ｄｅｖｅｌｏｓｉｌ ００５−５，１ＯＸ２５０ ｎ
ｕｎ）を用いた高速渣体クロマトグラフィー［溶出液０
．９ Ｍ ＮａＣｌ含有水メタノール（１：９）、ｉ速
３ ｍｌ／ ｍｉｎ、２１０ ｎｍｍ紫外線検出ココよ
って繰返し精製し、保持時間が２３分の画分（イ）、２
６分の画分（ロ）及び３０．５分の画分（ハ）を得た。274 mg of this white powder was added to an ODS column (Develosil 005-5,1OX250n manufactured by Nomura Chemical Co., Ltd.
High performance residue chromatography using un) [eluent 0
．． 9 M NaCl-containing water-methanol (1:9), i speed 3 ml/min, 210 nm ultraviolet light detection Coco was repeatedly purified, and the fraction with a retention time of 23 minutes (a), 2
A 6 minute fraction (b) and a 30.5 minute fraction (c) were obtained.
これ等画分から減圧下メタノールを除去後、クロロホル
ムで抽出し、抽出液を減圧下濃縮乾固して、夫々３１
Ｂの化合物（イ）、１１５ Ｂの化合物（ロ）及び２５
ｒａｇの化合物（ハ）を得た。After removing methanol from these fractions under reduced pressure, they were extracted with chloroform, and the extracts were concentrated to dryness under reduced pressure.
Compound B (a), 115 Compound B (b) and 25
rag compound (c) was obtained.
前記粗製物４１ ｍｇを、蟻酸２１及び水２ ｌｌの混
合液に溶解して１００℃で４時間反応させた後、減圧下
濃縮乾固し、残渣を逆相カラム（山村化学社製ＹＭＣ−
Ｐａｃｋ ＡＭ−３２４，ＩＯＸ ３００ ｍｓ）を用
い、０．５ ＄ＴＦＡ含有アセトニトリルー水（６：４
．流速４ ｍｌ／ ｍ１ｎ）を溶出液として紫外部吸収
（２２０ｎｍ）を検出しながら分離し、保持時間が６．
３分及び１３分の溶出画分を得た。41 mg of the crude product was dissolved in a mixture of 21 formic acid and 2 liters of water and reacted at 100°C for 4 hours, then concentrated to dryness under reduced pressure, and the residue was transferred to a reverse phase column (YMC-
Pack AM-324, IOX 300 ms) was used, and acetonitrile-water (6:4
．． Separation was carried out while detecting ultraviolet absorption (220 nm) using a flow rate of 4 ml/ml as an eluent, and the retention time was 6.
Elution fractions of 3 minutes and 13 minutes were obtained.
保持時間が１３分の溶出画分を減圧下濃縮乾固して７．
９ ｍｇの化合物（ニ）を得た。また、保持時間が６．
３分の溶出画分を減圧下濃縮乾固し、更に上記の逆相方
ラムにて、溶出液を０．５χ含有アセトニトリル−水（
１：Ｉ、流速３ ｍｌ／ｗｉｎ）に変えて分離し尿持時
間１０分の画分を集め、減圧下濃縮乾固して７．６ ｔ
ａｇの化合物（ホ）を得た。7. The eluted fraction with a retention time of 13 minutes was concentrated to dryness under reduced pressure.
9 mg of compound (d) was obtained. Also, the retention time is 6.
The 3-minute elution fraction was concentrated to dryness under reduced pressure, and the eluate was further diluted with 0.5χ-containing acetonitrile-water (
1:I, flow rate 3 ml/win), collected fractions with a urine retention time of 10 minutes, and concentrated to dryness under reduced pressure to yield 7.6 t.
Compound (e) of ag was obtained.
上記に得た化合物（イ）〜（ホ）は何れも、ニンヒドリ
ン反応が陰性、ドラーゲンドルフ反応が陽性であり、ま
た、６Ｎ塩酸中で２４時間加水分解すると以下のアミノ
酸を遊離する。Compounds (a) to (e) obtained above were all negative in the ninhydrin reaction and positive in the Dragendorff reaction, and also liberated the following amino acids when hydrolyzed in 6N hydrochloric acid for 24 hours.
β−アラニン、バリン、トレオニン、ロイシン、アロー
イソロイシン、Ｎ−メチルバリン、Ｎ−メチルアラニン
、Ｎ−メチルロイシン、Ｎ−メチルイソロイシン、Ｎ−
メチル−アローイソロイシン。β-alanine, valine, threonine, leucine, arrowisoleucine, N-methylvaline, N-methylalanine, N-methylleucine, N-methylisoleucine, N-
Methyl-arrow isoleucine.
化合物（イ）〜（ホ）の比旋光度、Ｕ■吸収スペクトル
、ＩＲ吸収スペクトル、マススペクトル（ＦＡＢＭＳ）
、１）Ｉ ＮＭＲ及び＋３ＣＮＭＲ等の測定結果は次の
通りである。Specific rotation, U absorption spectrum, IR absorption spectrum, mass spectrum (FABMS) of compounds (a) to (e)
, 1) The measurement results of I NMR and +3CNMR are as follows.
化合物（イ）：
無色粉末、融点１４７〜１５１℃
ＵＶ （ＣＨ３０Ｈ）λｍｓ＋＋＜２１Ｏｎ１１［α］
”−５７，２＠（ｃ＝０．２５．Ｃ）Ｉ３０）１）つ
ＦＡＢＭＳ 第１図の通り
ＩＲ（ＫＢｒ） 第２図の通り
ＩＨ−ＮＭＲ（ＣＤ３０Ｄ）第３図の通り化合ｖｌＪ（
ロ）：
無色粉末、融点１４９〜＋５４℃
ＬＩＶ （Ｃ）１３０Ｈ）λＩＩ＠Ｘ＜２１０ ｒｖ［
α コ２５−５９．０° （ｃ＝１．０．ＣＨ３０Ｈ）
フ
ＦＡＢＭＳ 第４図の通り
ＩＲ（にＯｒ） 第５図の通り
ＩＨ−ＮＭＲ（ＣＤ３０Ｄ）第６図の通り１３Ｃ−ＮＭ
Ｒ（ＣＤ３０Ｄ）第７図の通り化合物（ハ）：
無色粉末、融点１５６〜＋６０℃
ＵＶ （ＣＨ３０Ｈ）入ｓｅｘ＜２１０ ｒｖＣａ
１２５−５５．６°（ｃ＝０．２５．Ｃ）ｌｓＯＨ）
り
ＦＡＢＭＳ 第８図の通り
ＩＲ（にＢｒ） 第９図の通り
ＩＨ−ＮＭＲ（ＣＤ３００）第１０図の通り化合物（ニ
）
無色粉末、融点１４２〜１４８℃
ＵＶ （ＣＨ３０Ｈ）入ｓａｗ＜２１０ ｎｌｌＦ
ＡＢＭＳ 第１１図の通り
１）１−ＮＭＲ（ＣＤ３０Ｄ）第１２図の通り化合物（
ホ）
無色粉末、融点１１９〜１２４℃
ＬＩＶ （ＣＨｓＯＨ）λｓａｗ＜ ２１０ ｎｌＦＡ
８ＭＳ 第１３図の通り
ＩＨ−ＮＭＲ（ＣＤ３０Ｄ）第１４図の通り参考例
Ｎａ”、Ｋ” −ＡＴＰアーゼ阻害活性ブタ脳から抽出
したアデノシントリホスフ７ターゼ（Ｎａ會、に＋−Ａ
ＴＰアーゼ） ０．０２単位、ＮａＣ１１００ｍＭ、
２０ ｉＭのにＣ１，５ｍＭのＭｇＣ＋ ２及び５０１
ＩＩＭのトリス塩酸（ｐＨ７，４）を含む０．５ ｍｌ
の混合液を３７℃で５分間保持した。次いで被験物質を
加えて同温度で５分間保持した後、２ ｍＭのＡＴＰを
加えて更に５分間保持して酵素反応を行い、遊離した無
機リン酸をマーチン・ドティ法により定量し、被験物質
を加えない場合の対照実験値に対する相対酵素活性値を
求めた。Compound (A): Colorless powder, melting point 147-151°C UV (CH30H)λms++<21On11[α]
"-57,2@(c=0.25.C)I30) 1) FABMS As shown in Figure 1, IR (KBr) As shown in Figure 2, IH-NMR (CD30D) As shown in Figure 3, Compound vlJ (
B): Colorless powder, melting point 149-+54°C LIV (C) 130H) λII@X<210 rv[
α c25-59.0° (c=1.0.CH30H)
FABMS IR as shown in Figure 4 (Or) IH-NMR as shown in Figure 5 (CD30D) 13C-NM as shown in Figure 6
R (CD30D) As shown in Figure 7 Compound (c): Colorless powder, melting point 156~+60℃ UV (CH30H) included sex<210 rvCa
125-55.6° (c=0.25.C)lsOH)
FABMS as shown in Figure 8 IR (Br) as shown in Figure 9 IH-NMR (CD300) as shown in Figure 10 Compound (d) as shown in Figure 10 Colorless powder, melting point 142-148℃ UV (CH30H) included saw<210 nllF
ABMS As shown in Figure 11 1) 1-NMR (CD30D) As shown in Figure 12 Compound (
e) Colorless powder, melting point 119-124°C LIV (CHsOH) λsaw < 210 nlFA
8MS IH-NMR (CD30D) as shown in Figure 13 Reference example as shown in Figure 14 Na",K"-ATPase inhibitory activity Adenosine triphosph 7tase (Na, +-A) extracted from pig brain
TPase) 0.02 units, NaC 1100mM,
20 iM C1, 5mM MgC+2 and 501
0.5 ml containing IIM Tris-HCl (pH 7,4)
The mixture was held at 37°C for 5 minutes. Next, the test substance was added and held at the same temperature for 5 minutes, then 2 mM ATP was added and held for an additional 5 minutes to perform an enzymatic reaction, and the liberated inorganic phosphoric acid was quantified by the Martin-Doty method. Relative enzyme activity values were determined with respect to control experimental values without addition.
その結果、化合物（イ）（ロ）（ハ）は、１Ｏ−６〜３
×ｔｏ−５Ｍの濃度において、用量依存性にＮａ”、に
十−ＡＴＰアーゼの活性を阻害し、それ等の５０ ！阻
害濃度は夫々６Ｘ １０−””、 ６Ｘ ｔｏ−８Ｍ及
び８ＸｌＯ−’Ｍてあった。As a result, compounds (a), (b), and (c) are 1O-6 to 3
At concentrations of 5 to 5 M, Na' inhibited the activity of ni-ATPase in a dose-dependent manner, and their inhibitory concentrations were 6 to 10, 6 to 8 M, and 8 to 8 M, respectively. There was.
第１図は化合物（イ）のマススペクト、ル（ＦＡＢＭＳ
）、第２図は化合物（イ）のＩＲ吸収スペクトル（にＯ
ｒ）、第３図は化合物（イ）のＩＨ−ＮＭＲ（ＣＤ３０
Ｄ）スペクトルを夫々示し、第４図は化合物（ロ）のマ
ススペクトル（ＦＡＢＭＳ）、第５図は化合物（ロ）の
（Ｒ吸収スペクトル（にＢｒ）、第６図は化合物（ロ）
のＩＨ−ＮＭＲ（ＣＤ３０Ｄ）スペクトル、第７図は化
合物（ロ）の”Ｃ−ＮＭＲ（ＣｈＯＤ）スペクトルをを
夫々示し１、第８図は化合物（ハ）のマススペクトル（
ＦＡＢＭＳ）、第９図は化合物（ハ）のＩＲ吸収スペク
トル（ＫＢｒ）、第１０図は化合物（ハ）の１卜ＮＭＲ
（ＣＤ３０Ｄ）スペクトルを夫々示し、第１１図は化合
物（ニ）のマススペクトル（ＦＡＢＭＳ）、第１２図は
化合物（ニ）のＩＨ−ＮＭＲ（ＣＤ３０Ｄ）スペクトル
を夫々示し、第１３図は化合物（ホ）のマススペクトル
（ＦＡＢＭＳ）、第１４図は化合物（ホ）の’Ｈ−ＮＭ
Ｒ（ＣＤ３０Ｄ）スペクトルを夫々示す。
手続ネ巾正書（方式）
昭和６１年１０月６日Figure 1 shows the mass spectrum of compound (a).
), Figure 2 shows the IR absorption spectrum of compound (a)
r), Figure 3 shows the IH-NMR (CD30
D) The spectra are shown respectively. Figure 4 shows the mass spectrum (FABMS) of compound (b), Figure 5 shows the (R absorption spectrum (Br) of compound (b)), and Figure 6 shows the mass spectrum (Br) of compound (b).
Figure 7 shows the IH-NMR (CD30D) spectrum of compound (b), Figure 7 shows the C-NMR (ChOD) spectrum of compound (b), and Figure 8 shows the mass spectrum of compound (c).
FABMS), Figure 9 is the IR absorption spectrum (KBr) of compound (c), and Figure 10 is the 1-volume NMR of compound (c).
Figure 11 shows the mass spectrum (FABMS) of compound (d), Figure 12 shows the IH-NMR (CD30D) spectrum of compound (d), and Figure 13 shows the IH-NMR (CD30D) spectrum of compound (d). ) mass spectrum (FABMS), Figure 14 shows the 'H-NM of compound (e).
R (CD30D) spectra are shown respectively. Procedure book (method) October 6, 1986
Claims (1)
又は▲数式、化学式、表等があります▼（Ｂ）を示し、
Ｘ及びＹは夫々アラニン、β−アラニン、トレオニン、
ロイシン、バリン、イソロイシン、アロイソロイシン及
びこれ等アミノ酸のＮ−メチル置換体から構成されるペ
プチド鎖を示す） で表されるポリペプチド化合物。(1) Formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼-------(I) [In the formula, R is ▲There are mathematical formulas, chemical formulas, tables, etc.▼(A),
Or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ Indicates (B),
X and Y are alanine, β-alanine, threonine, respectively;
A polypeptide compound represented by the following formula (representing a peptide chain composed of leucine, valine, isoleucine, alloisoleucine, and N-methyl substituted products of these amino acids).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/119,573 US4782367A (en) | 1986-07-23 | 1987-11-12 | Extra data adding unit for a copier |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61-28330 | 1986-02-12 | ||
| JP2833086 | 1986-02-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS62277398A true JPS62277398A (en) | 1987-12-02 |
Family
ID=12245598
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61173457A Pending JPS62277398A (en) | 1986-02-12 | 1986-07-23 | Polypeptide compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS62277398A (en) |
-
1986
- 1986-07-23 JP JP61173457A patent/JPS62277398A/en active Pending
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