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Obtustatin

* Please kindly note that our products are not to be used for therapeutic purposes and cannot be sold to patients.

Obtustatin is an integrin α1β1 inhibitor with IC50 value of 0.8 nM for α1β1 binding to type IV collagen. Some research shows that it has antitumor efficacy in a synergistic mouse model of Lewis lung carcinoma.

Category

Peptide Inhibitors

Catalog number

BAT-006085

Molecular Formula

C184H284N52O57S8

Molecular Weight

4393.07

Size	Price	Stock	Quantity
1 mg	$519	In stock

Specification
Reference Reading

IUPAC Name

2-[(1R,1aS,4aS,6R,9R,9aS,12S,12aR,21S,23aS,24S,26aS,27R,32R,35S,38S,41S,47S,50S,56S,59S,62R,65S,68S,71S,74S,77S,80S,83S,86S,89S,92R,95S)-27-amino-1a,35,41,68-tetrakis(4-aminobutyl)-23a-(3-amino-3-oxopropyl)-26a-(3-carbamimidamidopropyl)-12a-[(2S)-2-[[(2S)-1-[[(2S)-1-[(2S)-2-(carboxymethylcarbamoyl)pyrrolidin-1-yl]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]-21,24,56,59,71,80,95-heptakis[(1R)-1-hydroxyethyl]-4a,74,83-tris(hydroxymethyl)-89-[(4-hydroxyphenyl)methyl]-86-(1H-imidazol-4-ylmethyl)-65-(1H-indol-3-ylmethyl)-50-methyl-38,77-bis(2-methylpropyl)-2a,5a,7a,8,10a,11,17,20,22a,23,25a,26,28a,33,36,39,42,48,51,54,57,60,63,66,69,72,75,78,81,84,87,90,93,96,99-pentatriacontaoxo-3,4,14a,15a,18a,19a,29,30-octathia-a,3a,6a,7,8a,10,11a,16,19,21a,22,24a,25,27a,34,37,40,43,49,52,55,58,61,64,67,70,73,76,79,82,85,88,91,94,97-pentatriacontazahexacyclo[60.44.10.86,32.49,92.012,16.043,47]octacosahectan-9a-yl]acetic acid

Synonyms

H-Cys(1)-Thr-Thr-Gly-Pro-Cys(2)-Cys(3)-Arg-Gln-Cys(1)-Lys-Leu-Lys-Pro-Ala-Gly-Thr-Thr-Cys(4)-Trp-Lys-Thr-Ser-Leu-Thr-Ser-His-Tyr-Cys(2)-Thr-Gly-Lys-Ser-Cys(3)-Asp-Cys(4)-Pro-Leu-Tyr-Pro-Gly-OH; L-cysteinyl-L-threonyl-L-threonyl-glycyl-L-prolyl-L-cysteinyl-L-cysteinyl-L-arginyl-L-glutaminyl-L-cysteinyl-L-lysyl-L-leucyl-L-lysyl-L-prolyl-L-alanyl-glycyl-L-threonyl-L-threonyl-L-cysteinyl-L-tryptophyl-L-lysyl-L-threonyl-L-seryl-L-leucyl-L-threonyl-L-seryl-L-histidyl-L-tyrosyl-L-cysteinyl-L-threonyl-glycyl-L-lysyl-L-seryl-L-cysteinyl-L-alpha-aspartyl-L-cysteinyl-L-prolyl-L-leucyl-L-tyrosyl-L-prolyl-glycine (1->10),(6->29),(7->34),(19->36)-tetrakis(disulfide)

Appearance

White Lyophilized Solid

Purity

98%

Sequence

CTTGPCCRQCKLKPAGTTCWKTSLTSHYCTGKSCDCPLYPG (Disulfide bridge: Cys1 and Cys10, Cys6 and Cys29, Cys7 and Cys34, Cys19 and Cys36)

Storage

Store at -20°C

Solubility

Soluble in Water (1 mg/mL)

InChI

InChI=1S/C184H284N52O57S8/c1-86(2)60-112-154(264)207-111(35-20-24-54-188)181(291)235-58-28-39-132(235)171(281)201-89(7)147(257)196-71-136(251)226-142(92(10)242)179(289)232-145(95(13)245)178(288)224-127-82-300-301-84-129(183(293)236-59-29-40-133(236)173(283)214-113(61-87(3)4)155(265)215-119(64-98-43-47-102(248)48-44-98)182(292)234-57-27-37-130(234)170(280)199-73-139(255)256)225-159(269)118(67-138(253)254)213-166(276)125-80-297-296-79-124-165(275)205-109(36-25-55-194-184(191)192)150(260)206-110(49-50-134(190)249)152(262)219-123(164(274)204-107(151(261)208-112)33-18-22-52-186)78-295-294-77-104(189)148(258)227-146(96(14)246)180(290)231-141(91(9)241)175(285)198-72-137(252)233-56-26-38-131(233)172(282)223-126(168(278)222-124)81-298-299-83-128(169(279)228-140(90(8)240)174(284)197-70-135(250)202-106(32-17-21-51-185)149(259)216-120(74-237)163(273)221-125)220-156(266)115(63-97-41-45-101(247)46-42-97)210-158(268)117(66-100-69-193-85-200-100)212-162(272)122(76-239)218-177(287)144(94(12)244)230-160(270)114(62-88(5)6)209-161(271)121(75-238)217-176(286)143(93(11)243)229-153(263)108(34-19-23-53-187)203-157(267)116(211-167(127)277)65-99-68-195-105-31-16-15-30-103(99)105/h15-16,30-31,41-48,68-69,85-96,104,106-133,140-146,195,237-248H,17-29,32-40,49-67,70-84,185-189H2,1-14H3,(H2,190,249)(H,193,200)(H,196,257)(H,197,284)(H,198,285)(H,199,280)(H,201,281)(H,202,250)(H,203,267)(H,204,274)(H,205,275)(H,206,260)(H,207,264)(H,208,261)(H,209,271)(H,210,268)(H,211,277)(H,212,272)(H,213,276)(H,214,283)(H,215,265)(H,216,259)(H,217,286)(H,218,287)(H,219,262)(H,220,266)(H,221,273)(H,222,278)(H,223,282)(H,224,288)(H,225,269)(H,226,251)(H,227,258)(H,228,279)(H,229,263)(H,230,270)(H,231,290)(H,232,289)(H,253,254)(H,255,256)(H4,191,192,194)/t89-,90+,91+,92+,93+,94+,95+,96+,104-,106-,107-,108-,109-,110-,111-,112-,113-,114-,115-,116-,117-,118-,119-,120-,121-,122-,123-,124-,125-,126-,127-,128-,129-,130-,131-,132-,133-,140-,141-,142-,143-,144-,145-,146-/m0/s1

InChI Key

XXWNADNJWWLFFP-MYXRGNOGSA-N

Canonical SMILES

CC1C(=O)NCC(=O)NC(C(=O)NC(C(=O)NC2CSSCC(NC(=O)C(NC(=O)C3CSSCC4C(=O)NC(C(=O)NC(C(=O)NC(CSSCC(C(=O)NC(C(=O)NC(C(=O)NCC(=O)N5CCCC5C(=O)NC(CSSCC(C(=O)NC(C(=O)NCC(=O)NC(C(=O)NC(C(=O)N3)CO)CCCCN)C(C)O)NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC2=O)CC6=CNC7=CC=CC=C76)CCCCN)C(C)O)CO)CC(C)C)C(C)O)CO)CC8=CNC=N8)CC9=CC=C(C=C9)O)C(=O)N4)C(C)O)C(C)O)N)C(=O)NC(C(=O)NC(C(=O)NC(C(=O)N2CCCC2C(=O)N1)CCCCN)CC(C)C)CCCCN)CCC(=O)N)CCCNC(=N)N)CC(=O)O)C(=O)N1CCCC1C(=O)NC(CC(C)C)C(=O)NC(CC1=CC=C(C=C1)O)C(=O)N1CCCC1C(=O)NCC(=O)O)C(C)O)C(C)O

1. Obtustatin: a potent selective inhibitor of alpha1beta1 integrin in vitro and angiogenesis in vivo

Dariusz G Kisiel, George P Tuszynski, Roy R Lobb, Cezary Marcinkiewicz, Shaker A Mousa, Juan J Calvete, Paul H Weinreb Cancer Res . 2003 May 1;63(9):2020-3.

A novel disintegrin, obtustatin, was purified from the venom of the Vipera lebetina obtusa viper. Obtustatin is the shortest disintegrin yet described, containing only 41 amino acids. It contains a similar pattern of cysteines to the short disintegrins echistatin and eristostatin but contains the sequence KTS rather than RGD in its active site loop. Obtustatin is a potent and selective inhibitor of alpha1beta1 integrin. It does not inhibit the closely related integrin alpha2beta1, nor a panel of other integrins tested. It does not inhibit ligand binding to the recombinant alpha1 I-domain. Importantly, obtustatin potently inhibited angiogenesis in vivo in the chicken chorioallantoic membrane assay, and in the Lewis lung syngeneic mouse model, it reduced tumor development by half, confirming and extending previous results on the relevance of alpha1beta1 integrin to angiogenesis and suggesting novel approaches to the generation of angiogenesis inhibitors.

2. Concerted motions of the integrin-binding loop and the C-terminal tail of the non-RGD disintegrin obtustatin

Bernardo Celda, Helena Kovacs, Daniel Monleon, Cezary Marcinkiewicz, M Paz Moreno-Murciano, Juan J Calvete J Biol Chem . 2003 Nov 14;278(46):45570-6. doi: 10.1074/jbc.M307030200.

Obtustatin is a potent and selective inhibitor of the alpha1beta1 integrin in vitro and of angiogenesis in vivo. It possesses an integrin recognition loop that harbors, in a lateral position, the inhibitory 21KTS23 motif. We report an analysis of the dynamics of the backbone and side-chain atoms of obtustatin by homonuclear NMR methods. Angular mobility has been calculated for 90 assigned cross-peaks from 22 off-resonance rotating frame nuclear Overhauser effect spectroscopy spectra recorded at three magnetic fields. Our results suggest that the integrin binding loop and the C-terminal tail display concerted motions, which can be interpreted by hinge effects. Among the integrin-binding motif, threonine 22 and serine 23 exhibit the lowest and the highest side-chain flexibility, respectively. It is noteworthy that the side chain of threonine 22 is not solvent-exposed, although based on synthetic peptides it appears to be the most critical residue for the inhibitory activity of obtustatin on the binding of integrin alpha1beta1 to collagen IV. Instead, the side chain of threonine 22 is oriented toward the loop center and hydrogen-bonded to residues Thr25 and Ser26. This network of interactions explains the restrained mobility of threonine 22 and suggests that its functional importance lies in maintaining the active conformation of the alpha1beta1 inhibitory loop.

3. The antitumor efficacy of monomeric disintegrin obtustatin in S-180 sarcoma mouse model

Sara Vaz, Naira Movsisyan, Elsa Logarinho, Luis Pardo, Narine Ghazaryan, Naira Ayvazyan, Joana Catarina Macedo Invest New Drugs . 2019 Oct;37(5):1044-1051. doi: 10.1007/s10637-019-00734-2.

Obtustatin, isolated from the Levantine Viper snake venom (Macrovipera lebetina obtusa -MLO), is the shortest known monomeric disintegrin shown to specifically inhibit the binding of the α1β1 integrin to collagen IV. Its oncostatic effect is due to the inhibition of angiogenesis, likely through α1β1 integrin inhibition in endothelial cells. To explore the therapeutic potential of obtustatin, we studied its effect in S-180 sarcoma-bearing mice model in vivo as well as in human dermal microvascular endothelial cells (HMVEC-D) in vitro, and tested anti-angiogenic activity in vivo using the chick embryo chorioallantoic membrane assay (CAM assay). Our in vivo results show that obtustatin inhibits tumour growth by 33%. The expression of vascular endothelial growth factor (VEGF) increased after treatment with obtustatin, but the level of expression of caspase 8 did not change. In addition, our results demonstrate that obtustatin inhibits FGF2-induced angiogenesis in the CAM assay. Our in vitro results show that obtustatin does not exhibit cytotoxic activity in HMVEC-D cells in comparison to in vivo results. Thus, our findings disclose that obtustatin might be a potential candidate for the treatment of sarcoma in vivo with low toxicity.