Peptide

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Cyclo(Prolylphenylalanyl-Epsilon-Aminocaproyl)

Basic information

Structure

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similarity structure
Molecular Formula

C20H27N3O3
Molecular Weight 357.2052417 g/mol
SMILES

RUN SEA Predictions

 O=C1NCCCCCC(=O)N2CCC[C@@H]2C(=O)N[C@H]1Cc1ccccc1  

PubChem|124750
InChI
InChI=1S/C20H27N3O3/c24-18-11-5-2-6-12-21-19(25)16(14-15-8-3-1-4-9-15)22-20(26)17-10-7-13-23(17)18/h1,3-4,8-9,16-17H,2,5-7,10-14H2,(H,21,25)(H,22,26)  
InChIKey
XLYAAACVHBCJDF-YSQOEHPSNA-N
2D Structure
PubChem|124750
3D Structure
PubChem|124750

Sequence

Graph alignment
Local alignment
IUPAC Condensed
cyclo[DL-Phe-Unk-DL-Pro]  

PubChem|124750
Amino acid chain
DL-Phe(1)--Unk--DL-Pro(1)  

CyclicPepedia|PP
Graph representation
DL-Phe,Unk,DL-Pro @0,2  

CyclicPepedia|PP
One letter code from Structure
PF  

CyclicPepedia|Struct2seq
Amino acid chain from Structure
Ac-Pro--C6:0  

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 357.2052417
Number of Rings 3.0
Complexity 0.961538462
XlogP3 AA 1.3951
Heavy Atom Count 26.0
Hydrogen Bond Donor Count 2.0
Hydrogen Bond Acceptor Count 3.0
Rotatable Bond Count 2.0
Property Name Property Value
Formal Charge 0.0
Refractivity 98.2894
Rule_of_Five 1.0
Number of Atoms 26.0
Topological Polar Surface Area 78.51
Refractivity 98.2894
Veber Rule 1.0
Ghose Filter 1.0
Property Name Property Value
RDKit Fingerprint
01000010100000100100100011010000010000100111010000100010000000000010101111101000100110000010110010000101000001001010001000110010000001001000110000001111100100000100001010000010000110001111000100100000001001001000000000000000010100000101001110001100011100101111000110001000000010001001000000000010010010010010001001000001010100000010111011010110101000000010011000000001000010000000000000000010010100000100000100001101000010000000101000110111110011100000000100010010111000010000000000000010001010010101100000101100110000000100100010010101100010000100100010010110001000000100010010001000000010111000101000110001000010011000100000001001100000100100000010100110000001000110001010100000000101001100011100010000100101000000000100100011001001011000100010000010001110101010001110010000000001100001001010001000001100001000100000001001111010110000010011101001000000110010011100000001000100000100111000000011001101000010111000010100011110011010000000011110001000001000010001010000011000010100001000000001010100000100000000100101001111110011110110001010100000001010000000001000101001100001000001000001110110000001001001010010000000101000000111001001010000000000101000001000100110100110100111001000010010011110000001000000000001001101010010100000011100010111000010010000100101000010101000000000000000010000110001001001011010100000000001100000100001000011101110000000010110110001010000010000000101001000001000000001000000001100000000000101100010001000000011111010001001001011000100000110010000100001010000101011011000000000100100100111000001100000001000010000010010100100000010100000000100100111001001000101000010000001000010000001000000100010110000000100000000000000010000000001000011000100001010000000000000000001011110000100100101000001010110001000100000100011011000010100000010010110100000000000100001010010000000000011111001101100000010110000011110100111110010000000000000000000110011100000010000001101101100000100101101000001010000010101000010000111110110000001011001011001001000000001001000100110000001000100100010000000000001101110000000000000111000000011
Morgan Fingerprint
0010100000100000000100000000000000000000001000000000000000000000100000000000000010000000001000000000000000000000000100000000000000000000000000000000000000000010000000000000000100000000000000000000000000000000000000000000000000000001000000000000000000000000000000000000000000000010000000001000000000000100010000100010000000000101000000000000100000000000000010000000000000000000000000000000010000000000000000000000000000000000000000001000000000100010000000001010000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000100000000000000010000000000000010000000000000000001000000000000000000000000000001000000000001000100000000000000000000000000010000000000000100000000000000000000000001000000000000000000000000000000000000000000010000001000000000000000000000000000000000000000000000000000000000000000000000000000010000000010000000000000000000001000000000000000000000000000000000000000000000000000000000000010000
MACCS Keys
00000000000000000000000000000000000000000000000000000010000000000000000000000001001101000011100110001100110000110000011011100001110110001110001100111011011110110111110

Sequence Properties

Property Name Property Value
Boman Index -1.49
Charge -0.00201570060725275

Manufacturers

Forecasting tools

Forecasting tools Value
Structure to Sequence
Structure Properties
Sequence to Structure
PF
Sequence Properties
PF
Expasy ProtParam Tool PF
SEA RUN SEA Predictions

Information Source

Reference

Pubmed_ID Title DOI Journal

1317746

 Cytotoxic analog of somatostatin containing methotrexate inhibits growth of MIA PaCa-2 human pancreatic cancer xenografts in nude mice 10.1016/0304-3835(92)90105-5.

Cancer Lett

Cytotoxic analog of somatostatin containing methotrexate inhibits growth of MIA PaCa-2 human pancreatic cancer xenografts in nude mice

Abstract

  • Nude mice bearing xenografts of MIA PaCa-2 human pancreatic cancer cell line were treated for 4 weeks with AN-51, a somatostatin octapeptide analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121) containing methotrexate attached to the alpha-amino group of D-Phe in position 1. Control groups of mice received saline, RC-121 or methotrexate. Drugs were given in equimolar doses by daily s.c. injections. After 7 days of treatment with 25 micrograms/day of AN-51, tumor growth was completely inhibited although the treatment had to be suspended because of toxic side effects, especially on the gastrointestinal tract, accompanied by major weight loss of the animals. Mice were allowed to recover for 1 week and treatment was continued with 12.5 micrograms/day AN-51. After 2 weeks of additional therapy, tumor volume, percentage change in tumor volume, and tumor weights were significantly decreased, compared with controls, only in the group treated with AN-51. Methotrexate and RC-121 also inhibited tumor growth, but their effects were not statistically significant. AN-51 retained its hormonal activity and decreased serum growth hormone levels in mice. Binding affinity of AN-51 for somatostatin receptors on MIA PaCa-2 cells was found to be 2.5-times lower than that of parent compound RC-121. This is the first report on inhibition of human pancreatic cancer growth in vivo by somatostatin analogs carrying cytotoxic radicals.

1975697

 Permeability of the murine blood-brain barrier to some octapeptide analogs of somatostatin 10.1073/pnas.87.17.6762.

Proc Natl Acad Sci U S A

Permeability of the murine blood-brain barrier to some octapeptide analogs of somatostatin

Abstract

  • Analogs of somatostatin are being investigated clinically for the treatment of various malignancies, including brain tumors. We studied the ability of three therapeutically promising radioactively labeled somatostatin octapeptide analogs, RC-160, RC-121, and RC-161, to cross the blood-brain barrier (BBB) after peripheral or central injection. After i.v. injection, intact RC-160 was recovered from the blood and the brain. The entry rates were different from each compound but were generally low. By contrast, entry across the intact BBB increased 220 times when RC-160 was given in a serum-free perfusate. This suggests that some serum-related factor, probably the previously described protein binding or an aggregation-promoting factor, is the main determinant in limiting the blood-to-brain passage of somatostatin analogs. Entry into the brain was not inhibited by the addition of unlabeled analog to the perfusate, showing that passage was probably by diffusion across the membranes that comprise the BBB rather than by saturable transport. By contrast, a saturable system was found to transport peptide out of the central nervous system (CNS). The clearance from the CNS of RC-160 and RC-121, but not RC-161, was faster than could be accounted for by reabsorption of cerebrospinal fluid. Transport of radioactively labeled RC-160 out of the CNS was inhibited by unlabeled RC-160 or somatostatin but was not affected by some other peptide known to cross the BBB by their own transport systems. More than 80% of the radioactivity recovered from the blood after intracerebroventricular injection of RC-160 was eluted by HPLC at the position of the labeled analog, showing that the peptide had crossed the BBB in intact form. Our results indicate the presence of a saturable transport system in one direction across the BBB for some superactive analogs of somatostatin.

2564678

 Somatostatin analogues inhibit growth of pancreatic cancer by stimulating tyrosine phosphatase 10.1073/pnas.86.6.2003.

Proc Natl Acad Sci U S A

Somatostatin analogues inhibit growth of pancreatic cancer by stimulating tyrosine phosphatase

Abstract

  • Several analogues of somatostatin were examined in the Mia PaCa-2 human pancreatic cancer cell line for their ability to promote tyrosine phosphatase activity affecting the receptors for the epidermal growth factor. The inhibition of growth of the Mia PaCa-2 cells in culture was also evaluated to determine the mechanism of action of somatostatin analogues and their relative effectiveness in inhibiting cancer growth. Of the analogues tested D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) caused the greatest stimulation of tyrosine phosphatase activity. Analogue D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121) had less effect but was more potent than somatostatin-14. Analogue D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr(ol) (SMS 201-995) produced no significant dephosphorylation. The analogues displayed the same order of activity in assays on growth inhibition of Mia PaCa-2 cells in cultures. Analogue (SMS-201-995) caused virtually no tyrosine phosphatase stimulation or growth inhibition in this cancer cell line, although it possesses a much higher antisecretory activity than somatostatin-14 in normal tissues. These observations indicate that somatostatin and some of its analogues can act as growth inhibitors in cancer cells through the activation of tyrosine phosphatase. These data reinforce the view that somatostatin analogue RC-160 and related compounds could be used for treatment of pancreatic cancer.