Basic information

CPKB ID	CP02045
IUPAC Name	(3S,6S,12R,15S,18S,21R,24R,27S,30S,33R)-6,18,30-trimethyl-3,9,12,15,21,24,27,33,36-nona(propan-2-yl)-1,7,13,19,25,31-hexaoxa-4,10,16,22,28,34-hexazacyclohexatriacontane-2,5,8,11,14,17,20,23,26,29,32,35-dodecone
Source	Streptomyces microflavus [Division : Bacteria] Taxonomy :1919 (Unassigned-Actinomycetota-Kitasatosporales-Actinomycetes-Streptomycetaceae Streptomyces) Wikipedia: Streptomyces microflavus PubChem
Information	Shiny crystalline solid. Used as an insecticide and nematocide. Not registered as a pesticide in the U.S. (EPA, 1998) Spiruchostatin C is a cyclodepsipeptide and a spiruchostatin. It has a role as a metabolite. PubChem\|131668508

Legend

Structure

Molecular Formula	C54H90N6O18
Molecular Weight	1110.63116 g/mol
SMILES RUN SEA Predictions	CC(C)C1NC(=O)[C@@H](C(C)C)OC(=O)[C@H](C(C)C)NC(=O)[C@H](C)OC(=O)[C@@H](C(C)C)NC(=O)[C@@H](C(C)C)OC(=O)[C@H](C(C)C)NC(=O)[C@H](C)OC(=O)[C@@H](C(C)C)NC(=O)C(C(C)C)OC(=O)[C@H](C(C)C)NC(=O)[C@H](C)OC1=O PubChem\|131668508
InChI	InChI=1S/C54H90N6O18/c1-22(2)34-49(67)73-31(19)43(61)55-38(26(9)10)53(71)77-41(29(15)16)47(65)59-36(24(5)6)51(69)75-33(21)45(63)57-39(27(11)12)54(72)78-42(30(17)18)48(66)60-35(23(3)4)50(68)74-32(20)44(62)56-37(25(7)8)52(70)76-40(28(13)14)46(64)58-34/h22-42H,1-21H3,(H,55,61)(H,56,62)(H,57,63)(H,58,64)(H,59,65)(H,60,66)/t31-,32-,33-,34+,35+,36?,37-,38-,39-,40+,41+,42?/m0/s1
InChIKey	FCFNRCROJUBPLU-HFYZFAIONA-N

2D Structure PubChem\|131668508

Sequence

IUPAC Condensed	cyclo[OAla-Val-D-OVal-D-Val-OAla-Val-D-OVal-DL-Val-OAla-Val-DL-OVal-D-Val] PubChem\|131668508
Amino acid chain	OAla(1)--Val--D-OVal--D-Val--OAla--Val--D-OVal--DL-Val--OAla--Val--DL-OVal--D-Val(1) CyclicPepedia\|PP
Graph representation	OAla,Val,D-OVal,D-Val,OAla,Val,D-OVal,DL-Val,OAla,Val,DL-OVal,D-Val @0,11 CyclicPepedia\|PP
Amino acid chain from Structure	Ac-Val(1)(2)--Ac-Val(1)(3)--Ac-Val(3)(4)--Ac-Val(4)(5)--Ac-Val(5)(6)--Ac-Val(2)(6) CyclicPepedia\|Struct2seq
svg Image PubChem\|131668508

Chemical and Physical Properties

Structure Properties

Property Name	Property Value
Exact Mass	1110.63116
Number of Rings	1.0
Complexity	0.230769231
XlogP3 AA	2.3433
Heavy Atom Count	78.0
Hydrogen Bond Donor Count	6.0
Hydrogen Bond Acceptor Count	18.0
Rotatable Bond Count	9.0

Property Name	Property Value
Formal Charge	0.0
Refractivity	281.4282
Rule_of_Five	0.0
Number of Atoms	78.0
Topological Polar Surface Area	332.4
Refractivity	281.4282
Veber Rule	0.0
Ghose Filter	0.0

Property Name	Property Value
RDKit Fingerprint	00100000000010100000110000110001100000000001100000101000100101010100000010000100000100000010000001000101000000111001001001110100010000100000000000000100000010010000001100000110110111000111000101000000000111001000100101001010000011000100000101000000010001001110010100001000000000100000001100000110000000001100100110000110110100100000000011010000000000100001001000100010000000000000000001100001000000000010000100001100001000110000100100111001101100001000000000000010010110000000010000001000000100010100010000100100000001110000010000000100100001010000100010001110001101001000010001101000000000000100110000000000000010010010010000001111000100100000000000101001010000000000000000000001010001000100011100101000000111100000010000000010000001000101000100010010001100100011001010010000000001011001000010000000001000001000000000110000110001000000101010000110000000001001100000000000000100000010011001001000110000101000100101000111001000010110000001010001100000001000011000010000011000010011000000010000010100010010000000000000001110000000000100010011100000100100010000110100001010000001000000000000100000000001001001000010000000110000000000001000000100000100101001101000001010101100101101000001000000000010000101100000010000000000011011100000011001000010011011000000000000001100000000110000100010000011000001101001010011100001000001000101000010000001111000101000010100110010000000100010100000000010011100000111000001001111110010100001100010100010000000000100000010110011010100000100010011001000000000000101000100000000110010111010000000000000000000010100001100000000010000000001101000010100001100001000100000000000000000000011110000001000001000100010010000010010010100001100000000000100000010010000010001010000010000000000100000000010000110100000100000100001001000010000000001010110101010001100000000010000000000001000100101000000000001010010010000000000000001000000000000000000010001000000000000000000010100101101101100001010010000000001000000010000011100010000010010011011000001000000000001110010000001001000000100010000000100000000100000001111100000011001
Morgan Fingerprint	0100000000100000000000000000000001000000000000000000000000000000000000000000000000000000001000000000000000000000000000000000000000000000000000000000110000000000000000000000000000000000000000000000001000000000000000000000010000000010000000000000000000000100000000000000000000000000000101000000000000000100000000000010000000000000000000000000000000000100000010000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000010001000001000000000000000000000000000000000000000000000000000000000000000000001000000000000000000000000000000000000000000000000000000000000000000010000000000000000000010000010000000000000000000000000000000000000000000000000000000000000000000000001000000000000000000001000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000100000000000000000000000000000000000000000000000000000000000000000000010000000000000000000000000000000000000000000001000000000000000000000000000000010000
MACCS Keys	00000000000000000000000000000000000000000000000000000000010000000000000010100000000000000000100100000000000000100000010011010001000100001100111100100111101011111100110

Binding Target

Other evidence

Property Name	Property ID
DrugMAP	DMW4TYV

Biologic Description

Toxicity PubChem|131668508

Neurotoxin - Other CNS neurotoxin

Manufacturers

Manufacturers Name	Value
CreativePeptides	Cyclo[Oala-Val-D-Oval-D-Val-Oala-Val-D-Oval-Dl-Val-Oala-Val-Dl-Oval-D-Val]
Bayer healthcare pharmaceuticals	Cyclo[Oala-Val-D-Oval-D-Val-Oala-Val-D-Oval-Dl-Val-Oala-Val-Dl-Oval-D-Val]
Upsher smith laboratories	Cyclo[Oala-Val-D-Oval-D-Val-Oala-Val-D-Oval-Dl-Val-Oala-Val-Dl-Oval-D-Val]
Merck	Cyclo[Oala-Val-D-Oval-D-Val-Oala-Val-D-Oval-Dl-Val-Oala-Val-Dl-Oval-D-Val]

Manufacturers Name	Value
Apotex	Cyclo[Oala-Val-D-Oval-D-Val-Oala-Val-D-Oval-Dl-Val-Oala-Val-Dl-Oval-D-Val]
Baxter Healthcare Corp	Cyclo[Oala-Val-D-Oval-D-Val-Oala-Val-D-Oval-Dl-Val-Oala-Val-Dl-Oval-D-Val]
Pharmasources	Cyclo[Oala-Val-D-Oval-D-Val-Oala-Val-D-Oval-Dl-Val-Oala-Val-Dl-Oval-D-Val]
Novartis	Cyclo[Oala-Val-D-Oval-D-Val-Oala-Val-D-Oval-Dl-Val-Oala-Val-Dl-Oval-D-Val]
AstraZeneca	Cyclo[Oala-Val-D-Oval-D-Val-Oala-Val-D-Oval-Dl-Val-Oala-Val-Dl-Oval-D-Val]

Forecasting tools

Forecasting tools	Value
Structure to Sequence	CC(C)C1NC(=O)[C@@H](C(C)C)OC(=O)[C@H](C(C)C)NC(=O)[C@H](C)OC(=O)[C@@H](C(C)C)NC(=O)[C@@H](C(C)C)OC(=O)[C@H](C(C)C)NC(=O)[C@H](C)OC(=O)[C@@H](C(C)C)NC(=O)C(C(C)C)OC(=O)[C@H](C(C)C)NC(=O)[C@H](C)OC1=O
Structure Properties	CC(C)C1NC(=O)[C@@H](C(C)C)OC(=O)[C@H](C(C)C)NC(=O)[C@H](C)OC(=O)[C@@H](C(C)C)NC(=O)[C@@H](C(C)C)OC(=O)[C@H](C(C)C)NC(=O)[C@H](C)OC(=O)[C@@H](C(C)C)NC(=O)C(C(C)C)OC(=O)[C@H](C(C)C)NC(=O)[C@H](C)OC1=O
Expasy ProtParam Tool
SEA	RUN SEA Predictions

Information Source

Property Name	Property ID
Patents	FCFNRCROJUBPLU-HFYZFAIONA-N
pubchem	131668508
Drugbank	Cyclo[Oala-Val-D-Oval-D-Val-Oala-Val-D-Oval-Dl-Val-Oala-Val-Dl-Oval-D-Val]
DRAMP3	Cyclo[Oala-Val-D-Oval-D-Val-Oala-Val-D-Oval-Dl-Val-Oala-Val-Dl-Oval-D-Val]
Uniprot	Cyclo[Oala-Val-D-Oval-D-Val-Oala-Val-D-Oval-Dl-Val-Oala-Val-Dl-Oval-D-Val]
Cybase	Cyclo[Oala-Val-D-Oval-D-Val-Oala-Val-D-Oval-Dl-Val-Oala-Val-Dl-Oval-D-Val]
CONOSERVER	Cyclo[Oala-Val-D-Oval-D-Val-Oala-Val-D-Oval-Dl-Val-Oala-Val-Dl-Oval-D-Val]
BindingDB	CC(C)C1NC(=O)[C@@H](C(C)C)OC(=O)[C@H](C(C)C)NC(=O)[C@H](C)OC(=O)[C@@H](C(C)C)NC(=O)[C@@H](C(C)C)OC(=O)[C@H](C(C)C)NC(=O)[C@H](C)OC(=O)[C@@H](C(C)C)NC(=O)C(C(C)C)OC(=O)[C@H](C(C)C)NC(=O)[C@H](C)OC1=O
CHEMBL	Cyclo[Oala-Val-D-Oval-D-Val-Oala-Val-D-Oval-Dl-Val-Oala-Val-Dl-Oval-D-Val]
CTD	Cyclo[Oala-Val-D-Oval-D-Val-Oala-Val-D-Oval-Dl-Val-Oala-Val-Dl-Oval-D-Val]
Wikipedia	Valinomycin
KEGG Compound/Drug	Cyclo[Oala-Val-D-Oval-D-Val-Oala-Val-D-Oval-Dl-Val-Oala-Val-Dl-Oval-D-Val]
CHEBI	FCFNRCROJUBPLU-HFYZFAIONA-N
EPA DSSTox	Cyclo[Oala-Val-D-Oval-D-Val-Oala-Val-D-Oval-Dl-Val-Oala-Val-Dl-Oval-D-Val]
FDA Global Substance Registration System (GSRS)	Cyclo[Oala-Val-D-Oval-D-Val-Oala-Val-D-Oval-Dl-Val-Oala-Val-Dl-Oval-D-Val]
DTP/NCI	Cyclo[Oala-Val-D-Oval-D-Val-Oala-Val-D-Oval-Dl-Val-Oala-Val-Dl-Oval-D-Val]
Chemspider	FCFNRCROJUBPLU-HFYZFAIONA-N
VARIDT	DR00334

Reference

Pubmed_ID	Title	DOI	Journal
15118082	Multidimensional signatures in antimicrobial peptides	10.1073/pnas.0401567101.	Proc Natl Acad Sci U S A
Multidimensional signatures in antimicrobial peptides Abstract Conventional analyses distinguish between antimicrobial peptides by differences in amino acid sequence. Yet structural paradigms common to broader classes of these molecules have not been established. The current analyses examined the potential conservation of structural themes in antimicrobial peptides from evolutionarily diverse organisms. Using proteomics, an antimicrobial peptide signature was discovered to integrate stereospecific sequence patterns and a hallmark three-dimensional motif. This striking multidimensional signature is conserved among disulfide-containing antimicrobial peptides spanning biological kingdoms, and it transcends motifs previously limited to defined peptide subclasses. Experimental data validating this model enabled the identification of previously unrecognized antimicrobial activity in peptides of known identity. The multidimensional signature model provides a unifying structural theme in broad classes of antimicrobial peptides, will facilitate discovery of antimicrobial peptides as yet unknown, and offers insights into the evolution of molecular determinants in these and related host defense effector molecules.
15616305	Antibacterial activity and specificity of the six human {alpha}-defensins	10.1128/AAC.49.1.269-275.2005.	Antimicrob Agents Chemother
Antibacterial activity and specificity of the six human {alpha}-defensins Abstract We developed a kinetic, 96-well turbidimetric procedure that is capable of testing the antimicrobial properties of six human alpha-defensins concurrently on a single microplate. The defensins were prepared by solid-phase peptide synthesis and tested against gram-positive bacteria (Staphylococcus aureus and Bacillus cereus) and gram-negative bacteria (Enterobacter aerogenes and Escherichia coli). Analysis of the growth curves provided virtual lethal doses (vLDs) equivalent to conventional 50% lethal doses (LD(50)s), LD(90)s, LD(99)s, and LD(99.9)s obtained from colony counts. On the basis of their respective vLD(90)s and vLD(99)s, the relative potencies of human myeloid alpha-defensins against S. aureus were HNP2 > HNP1 > HNP3 > HNP4. In contrast, their relative potencies against E. coli and E. aerogenes were HNP4 > HNP2 > HNP1 = HNP3. HD5 was as effective as HNP2 against S. aureus and as effective as HNP4 against the gram-negative bacteria in our panel. HD6 showed little or no activity against any of the bacteria in our panel, including B. cereus, which was highly susceptible to the other five alpha-defensins. The assay described provides a quantitative, precise, and economical way to study the antimicrobial activities of host-defense peptides. Its use has clarified the relative potencies of human alpha-defensins and raised intriguing questions about the in vivo function(s) of HD6.
19253295	Isolation, purification and de novo sequencing of TBD-1, the first beta-defensin from leukocytes of reptiles	10.1002/pmic.200800569.	Proteomics
Isolation, purification and de novo sequencing of TBD-1, the first beta-defensin from leukocytes of reptiles Abstract A novel peptide with antimicrobial activity was isolated from leukocytes of the European pond turtle Emys orbicularis and purified to homogeneity by preparative gel electrophoresis followed by reversed phase chromatography. It was highly active in vitro against Escherichia coli, Listeria monocytogenes, methicillin-resistant Staphylococcus aureus, and Candida albicans. The isolated peptide was sequenced de novo by tandem mass spectrometry using both collision-induced and electron-transfer dissociation in combination with different chemical derivatization techniques. The 40-residue peptide, called TBD-1 (turtle beta-defensin 1), represents the first defensin isolated from reptilian leukocytes. It contains three disulfide bonds and shows high structural similarities to beta-defensins isolated from birds and mammals.
34206990	Human Defensins Inhibit SARS-CoV-2 Infection by Blocking Viral Entry	10.3390/v13071246.	Viruses
Human Defensins Inhibit SARS-CoV-2 Infection by Blocking Viral Entry Abstract Innate immunity during acute infection plays a critical role in the disease severity of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and is likely to contribute to COVID-19 disease outcomes. Defensins are highly abundant innate immune factors in neutrophils and epithelial cells, including intestinal Paneth cells, and exhibit antimicrobial and immune-modulatory activities. In this study, we investigated the effects of human α- and β-defensins and RC101, a θ-defensin analog, on SARS-CoV-2 infection. We found that human neutrophil peptides (HNPs) 1-3, human defensin (HD) 5 and RC101 exhibited potent antiviral activity against pseudotyped viruses expressing SARS-CoV-2 spike proteins. HNP4 and HD6 had weak anti-SARS-CoV-2 activity, whereas human β-defensins (HBD2, HBD5 and HBD6) had no effect. HNP1, HD5 and RC101 also inhibited infection by replication-competent SARS-CoV-2 viruses and SARS-CoV-2 variants. Pretreatment of cells with HNP1, HD5 or RC101 provided some protection against viral infection. These defensins did not have an effect when provided post-infection, indicating their effect was directed towards viral entry. Indeed, HNP1 inhibited viral fusion but not the binding of the spike receptor-binding domain to hACE2. The anti-SARS-CoV-2 effect of defensins was influenced by the structure of the peptides, as linear unstructured forms of HNP1 and HD5 lost their antiviral function. Pro-HD5, the precursor of HD5, did not block infection by SARS-CoV-2. High virus titers overcame the effect of low levels of HNP1, indicating that defensins act on the virion. HNP1, HD5 and RC101 also blocked viral infection of intestinal and lung epithelial cells. The protective effects of defensins reported here suggest that they may be useful additives to the antivirus arsenal and should be thoroughly studied.