Somatostatin and analogues

Abraldes JG, Bosch J. Somatostatin and analogues in portal hypertension. Hepatology 2002 35(6) 1305-12. 

Examples of pharmaceutical proteins are insulin, glucagon, somatostatin and analogues, erythropoeietin and analogues, interferons, interleukins, monoclonal antibodies, gonadorefin and analogues, colony stimulating factors, antithrombotic medicines, vaccines. 

Biological Activities and Analogues. Somatostatin exerts some neurotropic actions, eg, as a tranquilizer and as a spontaneous motor activity depressor. It also lengthens barbiturate anesthesia time and induces sedation and hypothermia. These actions are consistent with the strong association between somatostatin and GABA in the primate cerebral cortex, 90—95% of somatostatin-positive ceHs also contain GABA (100). 

Figure 4.12. Dose-response curves ofsomatostatin and analogues on histamine secretionfrom purified rat peritoneal mast cells [171], Somatostatin (x), [D-Lys9]-somatostatin f0J, [D-Lys4]-somatostatin (O), [Tyr1 J-somatostatin (A), Des,[Ala, Gly2]-desamino-fCys3]-somatostatin (A), dihydrosomatostatin m). and bis-S-acetamidomethyldihydrosomatostatin (Q).

Alternatively, if the dehydroamino acid is C-terminal or is central in the peptide chain, then the oxazolone precursor to the dehydropeptide must be in position two in order to apply this methodology (Scheme 7.165). The requisite unsaturated 5(4//)-oxazolone intermediate 518 is obtained from the appropriate precursors following standard cyclization procedures and avoiding experimental conditions that would epimerize the chiral center. This methodology has been applied to access analogues of important peptides including dehydroaspartame, somatostatin, and dermorphin. In these cases, a dehydroamino acid was incorporated into the peptide backbone to study the relationship between conformational restriction and biological properties of the modified peptide. 

The methods presented in the sections above are all suitable for the synthesis of lanthionines as amino acid derivatives. However, a very important synthetic goal remains the synthesis of lanthionine-containing peptides, for example the synthesis of lantibiotics and other peptide analogues where lanthionine has replaced cystine. In the following Sections some syntheses of lanthionine-containing peptides comprising analogues of cystine peptides, such as enkephalin, somatostatin, and oxytocin are described. 

A (SCA) 1. HMPPA-pMeBHA (TFA) 2. Nbz-pMeBHA (HF) somatostatin and gramicidin S analogues BOP/HOBt, PyAOP/HOAt Kaiser test yield and purity depends on anchoring Xaa and handle [374]... 

Another newer synthetic compound, octerotride is a longer acting analogue of somatostatin and is used in acromegaly. 

Dizziness occurred in 7.4% of 68 patients randomized to somatostatin and 8.2% of 73 randomized to octreotide, both by rapid infusion, to control variceal bleeding, in which the effectiveness of somatostatin and its analogues is probably via a transient reduction in heart rate and cardiac output (13). 

Somatostatin and its analogues have been reported to be OP3 ( i) opioid receptor antagonists (57). Somatostatin infusions significantly reduced the effectiveness of morphine analgesia in a case report of three patients with cancer. 

Somatostatin and its synthetic analogue octreotide reduce portal pressure by decreasing splanchnic blood flow. Octreotide has the advantage of a longer duration of action so that it can be given as a bolus injection rather than the constant intravenous infusion needed for administration of somatostatin. Its can be used as an alternative to terlipressin, having similar efficacy and indications for use. 

Verheyden P, De Wolf E, Jaspers H, and Van Binst G. Comparing Conformations at Low Temperature and at High Viscosity. Conformational Study of Somatostatin and Two of its Analogues in Methanol and in Ethylene Glycol. Int J Peptide Protein Res 1994b 44 401—409. 

As part of the coordinated research project (CRP) on comparative evaluation of therapeutic radiopharmaceuticals, the ior-CEAl-(scFv)2 fragment and the somatostatin peptide analogues ior-P1394 and [DOTA,Tyr ]octreotate (DOTATATE) were evaluated as targeted agents. The results obtained from in vitro and in vivo studies deomonstrate the clinical usefulness of these radiolabelled biomolecules as radiotherapeutic agents. 

Fuji Y, Gonoi T, Yamada Y, Chihara K, Inagaki N, Seino S (1994) Somatostatin receptor subtype SSTR2 mediates the inhibition of high-voltage-activated calcium channels by somatostatin and its analogue SMS 201-995. FEBS Lett 355 117-120... 

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