AA sequence: Cys1-Thr-Thr-Gly-Pro-Cys6-Cys7-Arg-Gln-Cys10-Lys-Leu-Lys-Pro-Ala-Gly-Thr-Thr-Cys19-Trp-Lys-Thr-Ser-Leu-Thr-Ser-His-Tyr-Cys29-Thr-Gly-Lys-Ser-Cys34-Asp-Cys36-Pro-Leu-Tyr-Pro-Gly-OH
Disulfide bonds: Cys1-Cys10, Cys6-Cys29, Cys7-Cys34 and Cys19-Cys36
Length (aa): 41
Formula: C184H284N52O57S8
Molecular Weight: 4393.13 Da
Appearance: White lyophilized solid
Solubility: aqueous buffer
CAS number: not available
Source: Synthetic
Purity rate: > 97 %
Obtustatin
200 $ – 1. 190 $
Inhibitor of the binding of α1β1 integrin to collagen IV
Obtustatin is a 41 amino acid disintegrin peptide isolated from the venom of the Vipera lebetina obtusa. It is a potent (IC50 = 2 nM) and selective inhibitor of the binding of α1β1 integrin to collagen IV. Contrary to other known disintegrins, it does not contain the classical RGD sequence. Obtustatin does not show inhibitory activity toward other integrins, including α2β1, αIIbβ3, αvβ3, α4β1, α5β1, α6β1, and α9β1, α4β7 integrins. Obtustatin potently inhibits angiogenesis in chicken and in mouse model and reduces tumor development by half.
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Other desintegrin peptides from snake venoms have been discovered this past years containing RGD or non-RGD sequences. Desintegrins are promising compounds in cancer therapies or as anti-coagulant.
Contact us if you are looking for other desintegrin peptides.
Structural and dynamical properties of KTS-disintegrins: A comparison between Obtustatin and Lebestatin
Obtustatin and Lebestatin are lysine-threonine-serine (KTS)-disintegrins, which are a family of low molecular weight polypeptides present in many viperidae venoms and are potent and specific inhibitors of collagen-binding integrins. The integrin binding loop, harboring the (21) KTS(23) motif, and the C-terminal tail are known to be responsible for the selective binding to the α1β1 integrin. Despite a very high sequence homology (only two mutations are present in Lebestatin relative to Obtustatin, namely R24L and S38L), Lebestatin exhibits a higher inhibitory effect than Obtustatin on cell adhesion and cell migration to collagens I and IV. Here we show, by means of molecular dynamics simulations of the two polypeptides in aqueous solution, that Lebestatin possesses a higher flexibility of the C-terminal tail and a greater solvent accessibility of the integrin binding loop than Obtustatin. It may be hypothesized that these properties may contribute to the higher binding-affinity of Lebestatin to its biological partner. © 2012 Wiley Periodicals, Inc.
Daidone I, et al. (2013) Structural and dynamical properties of KTS-disintegrins: A comparison between Obtustatin and Lebestatin. Biopolymers. PMID: 23097229
Angiostatic activity of obtustatin as alpha1beta1 integrin inhibitor in experimental melanoma growth
The presented results show the effect of targeting of collagen receptor, alpha1beta1 integrin expressed on the endothelial cells on the development of experimental melanoma and pathological angiogenesis. Obtustatin, a snake venom KTS-disintegrin, was applied as a specific inhibitor of this integrin. This low molecular weight peptide revealed a potent therapeutic effect on melanoma progression in 2 animal systems, mouse and quail. Its oncostatic effect was related to the inhibition of angiogenesis. Obtustatin inhibited the neovascularization ratio on the CAM embryo of quail, which was pathologically induced by the developing tumor. The i.v. administration of obtustatin completely blocked cancer growth of MV3 human melanoma in nude mice. In B16F10 syngeneic mouse model treatment with the disintegrin revealed a lower effect, although the development of the tumor was significantly reduced for both dosages. The mechanism of obtustatin action is related to the blocking of microvascular endothelial cell proliferation, which undergoes apoptosis in caspase-dependent manner. Summarizing, we present studies of low molecular weight disintegrin, obtustatin as a potential therapeutic compound for treatment of melanoma that contain a high level of vascularization.
Brown MC, et al. (2008) Angiostatic activity of obtustatin as alpha1beta1 integrin inhibitor in experimental melanoma growth. Int J Cancer. PMID: 18712720
KTS and RTS-disintegrins: anti-angiogenic viper venom peptides specifically targeting the alpha 1 beta 1 integrin
Integrins alpha(1)beta(1) and alpha(2)beta(1) are highly expressed on the microvascular endothelial cells, and blocking of their adhesive properties significantly reduced the VEGF-driven neovascularization ratio and tumor growth in animal models. Hence, inhibitors of the alpha(1)beta(1) and alpha(2) beta(1) integrins, alone or in combination with antagonists of other integrins involved in angiogenesis (eg. alpha (v)beta(3), alpha(v)beta(5), and alpha(6)beta(4)), may prove beneficial in the control of tumor neovascularization. Viperidae snakes have developed in their venoms an efficient arsenal of integrin receptor antagonists. KTS-(obtustatin, viperistatin, lebestatin) and RTS- (jerdostatin) disintegrins represent viper venom peptides that specifically block the interaction of the alpha(1)beta (1) integrin with collagens IV and I in vitro and angiogenesis in vivo. The possible therapeutic approach towards tumor neovascularization by targeting the alpha (5)beta (1), alpha(v)beta(5) and alpha (v)beta(3) integrins with RGD-bearing disintegrins has been explored in a number of laboratories. Here we discuss structure-function correlations of the novel group of specific (K/R)TS-disintegrins targeting the alpha(1)beta(1) integrin.
Calvete JJ, et al. (2007) KTS and RTS-disintegrins: anti-angiogenic viper venom peptides specifically targeting the alpha 1 beta 1 integrin. Curr Pharm Des. PMID: 17979730
Amino acid sequence and homology modeling of obtustatin, a novel non-RGD-containing short disintegrin isolated from the venom of Vipera lebetina obtusa
Disintegrins represent a group of cysteine-rich peptides occurring in Crotalidae and Viperidae snake venoms, and are potent antagonists of several integrin receptors. A novel disintegrin, obtustatin, was isolated from the venom of the Vipera lebetina obtusa viper, and represents the first potent and selective inhibitor of the binding of integrin alpha(1)beta(1) to collagen IV. The primary structure of obtustatin contains 41 amino acids and is the shortest disintegrin described to date. Obtustatin shares the pattern of cysteines of other short disintegrins. However, in contrast to known short disintegrins, the integrin-binding loop of obtustatin is two residues shorter and does not express the classical RGD sequence. Using synthetic peptides, a KTS motif was identified as the integrin-binding sequence. A three-dimensional model of obtustatin, built by homology-modeling structure calculations using different templates and alignments, strongly indicates that the novel KTS motif may reside at the tip of a flexible loop.
Moreno-Murciano M.P., et al. (2003) Amino acid sequence and homology modeling of obtustatin, a novel non-RGD-containing short disintegrin isolated from the venom of Vipera lebetina obtusa. Protein Sci. PMID: 12538900
Obtustatin: a potent selective inhibitor of alpha1beta1 integrin in vitro and angiogenesis in vivo
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.
Marcinkiewicz C., et al. (2003) Obtustatin: a potent selective inhibitor of alpha1beta1 integrin in vitro and angiogenesis in vivo. Cancer Res. PMID: 12727812
NMR solution structure of the non-RGD disintegrin obtustatin
The solution structure of obtustatin, a novel non-RGD disintegrin of 41 residues isolated from Vipera lebetina obtusa venom, and a potent and selective inhibitor of the adhesion of integrin alpha(1)beta(1) to collagen IV, has been determined by two-dimensional nuclear magnetic resonance. Almost the whole set of chemical shifts for 1H, 13C and 15N were assigned at natural abundance from 2D homonuclear and heteronuclear 500 MHz, 600 MHz and 800 MHz spectra at pH 3.0 recorded at 298 K and 303 K. Final structural constraints consisted of 302 non-redundant NOE (95 long-range, 60 medium, 91 sequential and 56 intra-residue), four disulfide bond distances, five chi1 dihedral angles and four hydrogen bonds. The 20 conformers with lowest total energy had no NOE violations greater than 0.35A or dihedral angle violations greater than 12 degrees. The average root-mean-square deviation (RMSD) for backbone atoms of all residues among the 20 conformers was 1.1A and 0.6A for the 29 best-defined residues. Obtustatin lacks any secondary structure. Compared to all known disintegrin structures in which the RGD motif is located at the apex of an 11 residue hairpin loop, the active KTS tripeptide of obtustatin is oriented towards a side of its nine residue integrin-binding loop. The C-terminal tail is near to the active loop, and these two structural elements display the largest atomic displacements due to local conformational disorder. Double cross-peaks for W20, Y28 and H27 in the aromatic region of TOCSY spectra, local RMSD values for these residues, and positive cross-peaks in a ROESY spectrum (600 MHz, 100 ms mixing time), suggest that these residues act as a hinge allowing for the overall flexibility of the entire integrin-binding loop. These distinct structural features, along with its different electrostatic surface potential in relation to other known disintegrins, may confer to obtustatin its reported alpha(1)beta(1) integrin inhibitory selectivity.
Moreno-Murciano M.P., et al. (2003) NMR solution structure of the non-RGD disintegrin obtustatin. J. Mol. Biol. PMID: 12742023