Peptide

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(3S,9S)-1,7-Diazatricyclo[7.3.0.03,7]Dodecane-2,8-Dione

Basic information

Structure

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similarity structure
Molecular Formula

C10H14N2O2
Molecular Weight 194.1055277 g/mol
SMILES

RUN SEA Predictions

 O=C1[C@@H]2CCCN2C(=O)[C@@H]2CCCN12  

PubChem|736756
InChI
InChI=1S/C10H14N2O2/c13-9-7-3-1-5-11(7)10(14)8-4-2-6-12(8)9/h7-8H,1-6H2/t7-,8-/m0/s1  
InChIKey
BKASXWPLSXFART-YUMQZZPRNA-N
2D Structure
PubChem|736756
3D Structure
PubChem|736756

Sequence

Graph alignment
Local alignment
One letter code from Structure
PP  

CyclicPepedia|Struct2seq
Amino acid chain from Structure
Pro--Pro  

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 194.1055277
Number of Rings 3.0
Complexity 0.857142857
XlogP3 AA -0.018
Heavy Atom Count 14.0
Hydrogen Bond Donor Count 0.0
Hydrogen Bond Acceptor Count 2.0
Rotatable Bond Count 0.0
Property Name Property Value
Formal Charge 0.0
Refractivity 49.47
Rule_of_Five 1.0
Number of Atoms 14.0
Topological Polar Surface Area 40.62
Refractivity 49.47
Veber Rule 1.0
Ghose Filter 0.0
Property Name Property Value
RDKit Fingerprint
01000000000000000100100001011000010000000011010000100010000000000000100001101000100000000010110010000010000001001000000000110000000000000000111000001101100100100100001010000010000110000110100100000000001001001000000000000000000100000100001110000000011100101011000100001000000010001001000000000000011010010000001000000001010100000000001011010000100000000010001000000000000010000000000000000010000100000000000100001100000010000000100000100001100011000000000100000010011000000000000000000010000010010100100000100100110000000000000010010101000100000000100010000100001000000100010010001000000000010000001000100001000010011000000000001001000000100010000010100110000000000110000000100000000100000100011100000000000001000000000100100011001000010000000000000000001100101000001100010000000001100001001000001000001000001000000000000001110000000000010010000000000000000010000000000001000100000000111000000011000100000000111000000100011010011000000000010110000000000000010001010000011000010000001000000001010100000000000000000000001000000011000100000010100000000010000000000000001001100001000000001001110010000001000001010010000000000000000110001001010010000000001000001000100110100110100101000000000000011010000001000000000001010100000010100000011100010010000010000000100100000010001000000000000000100000000001001001010010100000000000100000100000010001100100000001010000110001010000010000000000000000000000000000000000001100000000000000100010000000000010001010001000001011000100000100010000100001000000011011011000000000100100000110000000100000000000010000000000100000000010100000000100100010001001000101100010010001000000000001000000000010100000000100000000000010010000000001000010000100000010000001000000000000011100000100100000000001010010000000100000100011001000000000000010010000100000000000100000010011000000000001111001000100000010000000011010100110010000000000100000000000100000100000010000001001101100000100101100000000010000010001000010000110000110000000010001001000000000000001001001100000000001000000100000000000000001101010000100000000000000000011
Morgan Fingerprint
0000110000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000001000000000000000000000000000000000000000000000000000000001001000000000100000000000010000000000000000000000000000000000000000010000000000000000000000000000000000000000000000000000000000000000000000000000000000000000010000000001000000000000000000000000000000000000000000000000001000000000000000000000000000000000000000000001000000000000000000000000000000000000000000000000000000000000000000000000000000000100000000000000010000000000000000000000000000000001000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000010000000010000000000000000000000000000000000000000000000000000000000000000000000000000000000010000
MACCS Keys
00000000000000000000000000000000000000000000000000000000000000000000000000000001000101000000100110101100010000110000011011100001110000001110001100011000011010110101110

Sequence Properties

Property Name Property Value
Charge -0.00201570060725275

Manufacturers

Forecasting tools

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

Information Source

Reference

Pubmed_ID Title DOI Journal

10487698

 Quantitative and functional expression of somatostatin receptor subtypes in human prolactinomas 10.1210/jcem.84.9.5962.

J Clin Endocrinol Metab

Quantitative and functional expression of somatostatin receptor subtypes in human prolactinomas

Abstract

  • Recently, it was demonstrated that somatostatin analogs preferential for the SSTR5 subtype suppress PRL release from prolactinoma cell cultures by 30-40%. These data supported the idea of somatostatin receptor subtype-specific control of PRL secretion in such tumors. The present study examines the quantitative profile of SSTRs messenger ribonucleic acid (mRNA) in 10 PRL-secreting tumors and correlates the expression with the ability of native somatostatins (SS14 and SS28), SSTR2 preferential analogs (octreotide and BIM-23197), and the SSTR5 preferential analog BIM-23268 to suppress PRL secretion. RT-PCR quantitative analysis showed a large predominance of SSTR5 mRNA [5648 +/- 1918 pg/pg glyceraldehyde-3-phosphate dehydrogenase (GAPDH)] vs. SSTR2 mRNA (148 +/- 83 pg/pg GAPDH). The SSTR1 transcript was also highly expressed in prolactinomas (1296 +/- 669 pg/pg GAPDH). SSTR5 mRNA expression correlated with PRL inhibition induced by both SRIF14 and SRIF28. Among the different analogs tested, only BIM-23268 produced inhibition of PRL release similar to that achieved with the native peptides. Its EC50 for PRL suppression was 0.28 +/- 0.10 nmol/L. No additive effects on PRL suppression were achieved by cotreatment of the tumor cells with SSTR2 and SSTR5 preferential analogs. In the same tumor cell cultures, quinagolide, a potent dopamine agonist, produced a dose-dependent inhibition of PRL with an EC50 at least 10 times lower than that of BIM-23268. Coincubation of quinagolide and BIM-23268, particularly in tumor cells resistant to dopamine agonist treatment, did not produce additive effects on PRL suppression. In conclusion, prolactinomas have a specific pattern of SSTR subtype mRNA expression (SSTR5 and SSTR1). SSTR5 expression is correlated to PRL regulation. These inhibitory effects are superimposable, at a higher concentration, to those of the dopamine agonists, but are not additive, particularly in the adenomas resistant to dopaminergic suppression of PRL release.

10690891

 Human somatostatin receptor subtypes in acromegaly: distinct patterns of messenger ribonucleic acid expression and hormone suppression identify different tumoral phenotypes 10.1210/jcem.85.2.6338.

J Clin Endocrinol Metab

Human somatostatin receptor subtypes in acromegaly: distinct patterns of messenger ribonucleic acid expression and hormone suppression identify different tumoral phenotypes

Abstract

  • Recently, studies using somatostatin (SRIF) analogs preferential for either the SRIF receptor 2 (SSTR2) or the SSTR5 subtype demonstrated a variable suppression of GH and PRL release from GH-secreting human adenomas. These data suggested the concept of SSTR subtype specificity in such tumors. In the present study the quantitative expression of messenger ribonucleic acid (mRNA) for the 5 SSTR subtypes and the inhibitory effects of SRIF14; SRIF28; octreotide; the SSTR2-preferential analog, BIM-23197; and the SSTR5-preferential analog, BIM-23268, on GH and PRL secretion were analyzed in cells cultured from 15 acromegalic tumors. RT-PCR analysis revealed a consistent pattern of SSTR2 and SSTR5 mRNA expression. SSTR5 mRNA was expressed at a higher level (1052 +/- 405 pg/pg glyceraldehyde-3-phosphate dehydrogenase) than SSTR2 mRNA (100 +/- 30 pg/pg glyceraldehyde-3-phosphate dehydrogenase). However, only SSTR2 mRNA expression correlated with the degree of GH inhibition induced by SRIF14, SRIF28, and BIM-23197. The SSTR5-preferential compound inhibited GH release in only 7 of 15 cases. In cells cultured from the 10 mixed adenomas that secreted both GH and PRL, RT-PCR analysis revealed a consistent coexpression of SSTR5, SSTR2, and SSTR1 mRNA. In all cases SRIF14, SRIF28, and the SSTR5-preferential analog, BIM-23268, significantly suppressed PRL secretion, with a mean maximal inhibition of 48 +/- 4%. In contrast, the SSTR2-preferential analogs, BIM-23197 and octreotide, were effective in suppressing PRL in only 6 of 10 cases. In cells cultured from adenomas taken from patients partially responsive to the SRIF analog, octreotide, partial additivity in suppressing both GH and PRL secretion was observed when the SSTR2- and SSTR5-preferring analogs, BIM-23197 and BIM-23268, were tested in combination. Our data show a highly variable ratio of the SSTR2 and SSTR5 transcripts, according to tumors. The SSTR2-preferring compound consistently inhibits GH release, whereas the SSTR5-preferring compound is the main inhibitor of PRL secretion. When both drugs are combined, the partial additivity observed in mixed GH- plus PRL-secreting adenomas may be of interest in the therapeutic approach of such tumors.

11052995

 Somatostatin receptor subtype-5 mediates inhibition of peptide YY secretion from rat intestinal cultures 10.1152/ajpgi.2000.279.5.G983.

Am J Physiol Gastrointest Liver Physiol

Somatostatin receptor subtype-5 mediates inhibition of peptide YY secretion from rat intestinal cultures

Abstract

  • Somatostatin-14 (S-14) and somatostatin-28 (S-28) bind to five distinct membrane receptors (SSTRs), but S-28 has higher affinity for SSTR-5. Whether S-28 acting through SSTR-5 regulates inhibition of peptide YY (PYY) secretion was tested in fetal rat intestinal cell cultures. S-28 and S-14 caused dose-dependent inhibition of PYY secretion stimulated by gastrin-releasing peptide, but S-28 was more potent than S-14 (EC(50) 0.04 vs. 13.2 nM). PYY was inhibited by two analogs with affinity for SSTR-5, BIM-23268 and BIM-23052, more potently than S-14 and as effectively as S-28. The SSTR-5 analog L-362855 suppressed PYY equivalent only to S-14, but the structurally related peptide L-372588 (Phe to Tyr at position 2) was equipotent to S-28, whereas L-372587 (Phe to Tyr at position 7) caused no inhibition. An SSTR-2 analog decreased PYY secretion similar to S-14, and an SSTR-3 analog was ineffective. PYY secretion stimulated by phorbol 12-myristate 13-acetate and by forskolin was also more potently suppressed by S-28 and the octapeptide SSTR-5 analogs. The results indicate that S-28 mediates inhibition of gastrin-releasing peptide-stimulated PYY secretion through activation of SSTR-5 and includes suppression of cAMP- and protein kinase C-dependent pathways. Substitution of a single hydroxyl group confers differences in SSTR-5 agonist properties, suggesting region specificity for the intrinsic activity of this receptor subtype.