Peptide

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Cubicin

Basic information

CPKB ID CP01057
IUPAC Name
(3S)-3-[[(2S)-4-amino-2-[[(2S)-2-(decanoylamino)-3-(1H-indol-3-yl)propanoyl]amino]-4-oxobutanoyl]amino]-4-[[(3S,6S,9R,15S,18R,21S,24S,30S,31R)-3-[2-(2-aminophenyl)-2-oxoethyl]-24-(3-aminopropyl)-15,21-bis(carboxymethyl)-6-[(2R)-1-carboxypropan-2-yl]-9-(hydroxymethyl)-18,31-dimethyl-2,5,8,11,14,17,20,23,26,29-decaoxo-1-oxa-4,7,10,13,16,19,22,25,28-nonazacyclohentriacont-30-yl]amino]-4-oxobutanoic acid
Synonyms
(2S)-Daptomycin
060D533
103060-53-3
Akos005146218
Chebi:600103
Chembl387675
Cidecin
Cubicin
Dapcin
Daptomicina
Daptomycin
Daptomycine
Daptomycinum
Dapzura-Rt
Gtpl10904
Ly-146032
Ly146032
Ly-164032
Mfcd08282794
N-Decanoyl-L-Tryptophyl-L-Asparaginyl-L-Aspartyl-L-Threonylglycyl-L-Ornithyl-L-Aspartyl-D-Alanyl-L-Aspartylglycyl-D-Seryl-Threo-3-Methyl-L-Glutamyl-3-Anthraniloyl-L-Alanine-1.13-3.4-Lactone
N-Decanoyl-L-Tryptophyl-L-Asparaginyl-L-Aspartyl-L-Threonylglycyl-L-Ornithyl-L-Aspartyl-D-Alanyl-L-Aspartylglycyl-D-Seryl-Threo-3-Methyl-L-Glutamyl-3-Anthraniloyl-L-Alanine-Epsilon(1)-Lactone
N-Decanoyl-L-Tryptophyl-L-Asparaginyl-N-[(3S,6S,9R,15S,18R,21S,24S,30S,31R)-3-[2-(2-Aminophenyl)-2-Oxoethyl]-24-(3-Aminopropyl)-15,21-Bis(Carboxymethyl)-6-[(2R)-1-Carboxypropan-2-Yl]-9-(Hydroxymethyl)-18,31-Dimethyl-2,5,8,11,14,17,20,23,26,29-Decaoxo-1-Ox
N-Decanoyl-L-Tryptophyl-L-Asparaginyl-N-[(3S,6S,9R,15S,18R,21S,24S,30S,31R)-3-[2-(2-Aminophenyl)-2-Oxoethyl]-24-(3-Aminopropyl)-15,21-Bis(Carboxymethyl)-6-[(2R)-1-Carboxypropan-2-Yl]-9-(Hydroxymethyl)-18,31-Dimethyl-2,5,8,11,14,17,20,23,26,29-Decaoxo-1-Oxa-4,7,10,13,16,19,22,25,28-Nonaazacyclohentriacontan-30-Yl]-L-Alpha-Asparagine
Q-200927
Q63413234
Schembl28102
Sr-01000872587
Sr-01000872587-1
Source

Streptomyces filamentosus [Division : Bacteria]

Taxonomy :67294 (Unassigned-Actinomycetota-Kitasatosporales-Actinomycetes-Streptomycetaceae Streptomyces)  

Wikipedia: Streptomyces filamentosus

PubChem  

Function

Anti-Biotics   Anti-Gram+   PubChem  

Information

Cubicin is a natural product found in Streptomyces filamentosus with data available. Daptomycin is a polypeptide comprising N-decanoyltryptophan, asparagine, aspartic acid, threonine, glycine, ornithine, aspartic acid, D-alanine, aspartic acid, glycine, D-serine, threo-3-methylglutamic acid and 3-anthraniloylalanine (also known as kynurinine) coupled in sequence and lactonised by condensation of the carboxylic acid group of the 3-anthraniloylalanine with the alcohol group of the threonine residue. It has a role as an antibacterial drug, a bacterial metabolite and a member of calcium-dependent antibiotics. It is a lipopeptide, a macrolide, a heterodetic cyclic peptide, a macrocycle and a lipopeptide antibiotic. Daptomycin is an intravenously administered, broad spectrum antibiotic used to treat complex skin and tissue infections, endocarditis and bacteremia. Daptomycin is associated with a low to modest rate of serum enzyme elevations during therapy, but is a very rare cause of clinically apparent liver injury.

PubChem|16134395  

Legend

Structure

Download structure
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similarity structure
Molecular Formula

C72H101N17O26
Molecular Weight 1619.710366 g/mol
SMILES

RUN SEA Predictions

 CCCCCCCCCC(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H]1C(=O)NCC(=O)N[C@@H](CCCN)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C)C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@H](CO)C(=O)N[C@@H]([C@H](C)CC(=O)O)C(=O)N[C@@H](CC(=O)c2ccccc2N)C(=O)O[C@@H]1C  

PubChem|16134395
InChI
InChI=1S/C72H101N17O26/c1-5-6-7-8-9-10-11-22-53(93)81-44(25-38-31-76-42-20-15-13-17-39(38)42)66(108)84-45(27-52(75)92)67(109)86-48(30-59(102)103)68(110)89-61-37(4)115-72(114)49(26-51(91)40-18-12-14-19-41(40)74)87-71(113)60(35(2)24-56(96)97)88-69(111)50(34-90)82-55(95)32-77-63(105)46(28-57(98)99)83-62(104)36(3)79-65(107)47(29-58(100)101)85-64(106)43(21-16-23-73)80-54(94)33-78-70(61)112/h12-15,17-20,31,35-37,43-50,60-61,76,90H,5-11,16,21-30,32-34,73-74H2,1-4H3,(H2,75,92)(H,77,105)(H,78,112)(H,79,107)(H,80,94)(H,81,93)(H,82,95)(H,83,104)(H,84,108)(H,85,106)(H,86,109)(H,87,113)(H,88,111)(H,89,110)(H,96,97)(H,98,99)(H,100,101)(H,102,103)/t35-,36-,37-,43+,44+,45+,46+,47+,48+,49+,50-,60+,61+/m1/s1  
InChIKey
DOAKLVKFURWEDJ-WAPNNJSTNA-N
2D Structure
PubChem|16134395

Sequence

Graph alignment
Local alignment
IUPAC Condensed
decanoyl-Trp-Asn-Asp-Thr(1)-Gly-Orn-Asp-D-Ala-Asp-Gly-D-Ser-Glu(3R-Me)-Asp(Ph(2-NH2))-(1)  

PubChem|16134395
Amino acid chain
decanoyl--Trp--Asn--Asp--Thr(1)--Gly--Orn--Asp--D-Ala--Asp--Gly--D-Ser--Glu(3R-Me)--Asp(Ph(2-NH2))(1)  

CyclicPepedia|PP
Graph representation
decanoyl,Trp,Asn,Asp,Thr,Gly,Orn,Asp,D-Ala,Asp,Gly,D-Ser,Glu(3R-Me),Asp(Ph(2-NH2)) @4,13  

CyclicPepedia|PP
One letter code from Structure
WNDTGADADGSIA  

CyclicPepedia|Struct2seq
Amino acid chain from Structure
Ac-Trp--Asn--Asp--Thr(1)--Gly--Orn--Asp--Ala--Asp--Gly--Ser--3Me-Glu--CO(1)  

CyclicPepedia|Struct2seq
Description of the conversion sequence The one letter code and Amino acid chain derived from the structural transformation may be inconsistent, with the Amino acid chain containing Essential Amino acid and the one letter code not.

Chemical and Physical Properties

CyclicPepedia|Struc2Seq + PP

Structure Properties

Property Name Property Value
Exact Mass 1619.710366
Number of Rings 4.0
Complexity 0.547826087
XlogP3 AA -5.6218
Heavy Atom Count 115.0
Hydrogen Bond Donor Count 22.0
Hydrogen Bond Acceptor Count 24.0
Rotatable Bond Count 35.0
Property Name Property Value
Formal Charge 0.0
Refractivity 400.2605
Rule_of_Five 0.0
Number of Atoms 115.0
Topological Polar Surface Area 702.02
Refractivity 400.2605
Veber Rule 0.0
Ghose Filter 0.0
Property Name Property Value
RDKit Fingerprint
11100111110110101111110111110000111011101111100000111111111111101110101110101101111111010111100011110111110101111111011001110111010001111101111100011111001110010111001100011111110111001111001101110110101101101000000111000111010111000101010110101111011111101111000110011110001111101111111101000010000011111111100111010111110101110011111110010110111100011001111101001011111001000001111001111011000101000111100101001110010011110101101100111011111110100100011001010110111010111110010010001110001101010111110100101101011101111110110111001101101011100111100011011110101101111110010111111101011110111100101110111001110010011011110000111111110100101101101111110111111011010110111110111111010111011001011100111000100111100000010100011010101101110111111010010010011110101010111111010010000111011011011010011011011100011010111010111001111011110000101011101110111001110101111100100111110110101111101001111111111101101110111101110111011100010110110001011100111110011001111110010010011001010110001001111011110101001111011000111101111111111111111110111111110001101111010101101110111001100011010001100001110110101101011101100010001001111110011111101101010001011100111001111001101111110000101111011101011011011110100111111101110100001101010111100110111111010111111011011001100101101110101110011011110001011111111100111001111111111101101111000101100011011111111111101011011110110111110011110111111101101111111110011111011101011111111011101101100111101010011001111110110011111111111111111111111110110001110000111111111110000000110110110011101111100111011101010100111111110100010100100011101100011101001111011101100010000011110111101011111010100100111110111010010000011010010110011111000111010110010011111100010001110011111111110100111101000111000111101001100001110111011011011101111011010111101010000110100001111110100010101011111111101100100101111110111110100111111010001011110001011001011111111010010101001101111110111111111101011111011011010111011110011111110111010111111011011101011011011011101111110111001101111100110110010000001111101100010010100101011101011111
Morgan Fingerprint
0100000000100000000000000000000001000000010000010000000000000000100000000000000110000010001000000000010000000000000101010000000010100000000010000001000000000000000000000100000100000000000000000000000000010000000000000000001000000000010000000001000000100000000001010010000000000000000101000000001000000100001000000010000000000100100001000000000000000000000110000000100000000000100000000001010000000000000000000000000000001001000000000101000010000000000000000000000000000000000000000010000000001110000000010000000000000001000000000000000000011000000001010000000000000000000001000000000101000001100000000000000000000000000000000000000000000000000000001010000010000000010001000000000000001000000000100100000000000000010100000010001010000000100000000000001000000011000000000000000000000000000000000010000000000011000000001000000000000000100000000010000001000001001000001000000000110000000000010000010100000000000000100100000000000010000000000000010000100100011000000000000100000000000001001000000010001010010010100100000000010000
MACCS Keys
00000000000000000000000000000000000000000000000000000110010000000100000000000001101110000111100111001100110011110011111011010101110111011111111111110111111111111111110

Sequence Properties

Property Name Property Value
Boman Index 1.86230769230769
Instability -18.9615384615384
Charge -3.00067624814223
Aliphatic Index 53.076923076923

Binding Target

Other evidence

Property Name Property ID
TTD D05HPI
DrugMAP DMFDQ3I DMKDU16

Biologic Description

Toxicity PubChem|16134395

Elevations in serum aminotransferase levels occur in 2% to 6% of patients receiving daptomycin, rates that are minimally higher than with placebo or comparator drugs. The elevations are generally mild-to-moderate, asymptomatic and self-limited, frequently resolving without discontinuation or even interruption of therapy. Isolated case reports of possible liver injury from daptomycin have been reported, but serum bilirubin was normal in most cases, and the serum aminotransferase elevations were mild-to-moderate and typically accompanied by severe muscle injury with marked CK elevations. Such cases without jaundice or alkaline phosphatase elevations are more likely due to muscle rather than liver injury. Nevertheless, a few case reports of mild jaundice with a hepatocellular pattern of serum enzyme elevations and normal CK levels has been published. The latency to onset was 5 weeks, immunoallergic and autoimmune features were not present, and resolution was slow with mild abnormalities still present 6 weeks later. Thus, clinically apparent liver injury from daptomycin probably occurs, but is quite rare.

Manufacturers

Manufacturers Name Value
CreativePeptides
Bayer healthcare pharmaceuticals
Upsher smith laboratories
Merck
Manufacturers Name Value
Apotex
Baxter Healthcare Corp
Pharmasources
Novartis
AstraZeneca

Forecasting tools

Information Source

Reference

Pubmed_ID Title DOI Journal

11181894

 Comparative specificity of platelet alpha(IIb)beta(3) integrin antagonists

None

J Pharmacol Exp Ther

Comparative specificity of platelet alpha(IIb)beta(3) integrin antagonists

Abstract

  • Several platelet alpha(IIb)beta(3) integrin antagonists have been designed as preventive agents against the formation of arterial thrombi. Although the potency of these compounds in inhibiting platelet aggregation is in the nanomolar range, their specificity on other integrins that can bind ligands through an arginine-glycine-aspartic acid (RGD) motif is far from being well established. For instance, some cyclic RGD peptides can also interact with alpha(v)beta(3) integrin. We used a novel pharmacological assay, based on SDS-stable interaction between (125)I-echistatin and RGD-dependent integrins, to evaluate the specificity of several RGD compounds on integrins present on rat cardiac fibroblasts and human skin fibroblasts. of the RGD peptidomimetics tested (L-734,217, lamifiban, Ro 44-3888, SR 121566A, BIBU-52, XV459) could interact with either alpha(v)beta(3) and alpha(8)beta(1) on rat fibroblasts or with alpha(v)beta(3) and alpha(v)beta(1) on human fibroblasts. Cyclic RGD peptides showed some potency (3-80 microM) on rat and human integrins with an alpha(v) subunit. We also compared the potency of these compounds on platelets. All RGD compounds demonstrated IC(50) between 0.6 and 530 nM on basal human platelets. Activation of the receptor with thrombin resulted in a 2- to 60-fold increase in potency, with L-734,217 and BIBU-52 showing the largest difference. On basal and thrombin-activated rat platelets, only eptifibatide, DMP728, and XJ735 could displace (125)I-echistatin (IC(50) approximately 0.1-1.5 microM). These results indicate that RGD peptidomimetics have a specificity limited to alpha(IIb)beta(3) integrin, whereas cyclic RGD peptides can also interact with other RGD-dependent integrins, particularly those of the alpha(v) subunit family.

8874387

 Antagonists of integrin alpha v beta 3 inhibit retinal neovascularization in a murine model

None

Lab Invest

Antagonists of integrin alpha v beta 3 inhibit retinal neovascularization in a murine model

Abstract

  • Integrin alpha v beta 3 is differentially expressed in angiogenic blood vessels in skin granulation tissue, and alpha v beta 3 antagonists inhibit angiogenesis in chick chorioallantoic membranes. In this study, we investigated the role of alpha v beta 3 in retinal neovascularization. There was no detectable signal for alpha v beta 3 by immunohistochemistry in normal human retina, but neovascular tissue removed from the surface of the retina of patients with diabetic retinopathy showed intense staining for alpha v beta 3 within the endothelial cells of new blood vessels. In a murine model of oxygen-induced ischemic retinopathy, there was intense staining for alpha v beta 3 in endothelial cells participating in neovascularization but no detectable staining in normal retinal blood vessels of adult mice. Synthetic peptides that bind alpha v beta 3 and perturb alpha v beta 3-mediated adhesion in vitro inhibited retinal neovascularization in the murine model when given by intraperitoneal or periocular injections. These data suggest that alpha v beta 3 antagonists may provide a useful adjunct for the treatment of retinal neovascularization.

9534862

 Selective alpha v beta 3 integrin blockade potently limits neointimal hyperplasia and lumen stenosis following deep coronary arterial stent injury: evidence for the functional importance of integrin alpha v beta 3 and osteopontin expression during neointima formation 10.1016/s0008-6363(97)00184-3.

Cardiovasc Res

Selective alpha v beta 3 integrin blockade potently limits neointimal hyperplasia and lumen stenosis following deep coronary arterial stent injury: evidence for the functional importance of integrin alpha v beta 3 and osteopontin expression during neointima formation

Abstract

  • Lumen loss from vascular restenosis remains a leading cause of chronic revascularization failure.\n \n \n \n \n We hypothesized that cell-matrix adhesion, migration, and differentiation events that underlie restenosis are mediated by alpha v beta 3 integrin-ligand interactions.\n \n \n \n \n Using immunohistochemistry and in situ hybridization, we examined the spatial and temporal vessel wall expression of alpha v beta 3 and osteopontin following deep coronary arterial injury. Cell migration and adhesion assays were performed to demonstrate the affinity and specificity of XJ 735 for various vessel wall integrins. The effects of XJ 735 (a selective cyclic Arg-Gly-Asp (RGD) peptidomimetic alpha v beta 3 antagonist) on neointimal hyperplasia and lumen stenosis were tested in a porcine coronary injury model. Normolipemic swine underwent oversized stent injury followed by XJ 735 administration (9 animals, 28 lesions; 1 mg/kg bolus + 7 days 4 mg/kg/d infusion + 21 days 2 mg/kg i.v. bolus 12 hourly) or placebo (10 animals, 30 arterial lesions).\n \n \n \n \n Maximal alpha v beta 3 immunoreactivity was observed between 7-14 days following injury in the neointima, media, and adventitia. Maximal osteopontin mRNA signal in the neointima, media, and adventitia was observed at 14, 7 and 28 days respectively. IC50 for XJ 735 alpha v beta 3-mediated inhibition of human and porcine endothelial cell adhesion, and vascular smooth muscle cell migration, ranged from 0.6 to 4.4 microM. In contrast, IC50 for porcine or human alpha IIb/beta 3, alpha 4 beta 1, alpha v beta 5, and alpha 5 beta 1 inhibition exceeded 100 microM. Steady state XJ 735 plasma levels exceeded 5 microM. Despite slightly higher injury scores in XJ 735 treated animals, significant reductions in mean neointima area (43% reduction; p = 0.0009), and mean percent lumen stenosis (approximately 2.9 fold reduction; p = 0.04) were observed in XJ 735 treated animals. XJ 735 treatment did not significantly alter the relative size of the arterial injury and reference sites (geometric remodeling). Comparison of neontima area vs. injury score regression lines revealed significant reductions in slope (p = 0.0001) and intercept (p = 0.0001) for XJ 735.\n \n \n \n \n Selective alpha v beta 3 blockade is an effective anti-restenosis strategy that potently limits neointimal growth and lumen stenosis following deep arterial injury. The co-ordinate spatial and temporal upregulation of alpha v beta 3 expression following vessel wall injury, and the high affinity and specificity of XJ 735 for alpha v beta 3, confirms the importance of this integrin in adhesive and migratory cell-matrix events underlying coronary restenosis.