Somatostatin Receptor 1 Selective Analogues:  4. Three-Dimensional Consensus Structure by NMR

Grace, Christy R.; Durrer, L.; Koerber, Steven C.; Érchegyi, Judit; Reubi, Jean Claude; Rivier, Jean; Riek, Roland

doi:10.1021/jm049518u

Cited by 29 publications

(68 citation statements)

References 43 publications

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“…Many models for the bioactive conformation required for selective recognition by the somatostatin receptor subtypes have been proposed. 32,[47][48][49][50] The results reported here should allow a better definition of the D-Trp orientation in these models and exclude the gauche (+) 1 orientation.…”

Section: Resultsmentioning

confidence: 90%

Highly Potent 4-Amino-indolo[2,3-c]azepin-3-one-Containing Somatostatin Mimetics with a Range of sst Receptor Selectivities

et al. 2008

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The synthesis, biological evaluation, and conformational analysis of 4-amino-indolo[2,3-c]azepin-3-one (Aia)-containing SRIF mimetics are reported. Different subtype selectivities are observed depending on the N- and C-terminal substituents of the D-Aia-Lys dipeptide mimetic. An sst(5)-selective analogue with subnanomolar binding affinity was obtained that is the most potent agonist reported to date. A nonselective mimetic with high potency was also identified. This study allows a better definition of the bioactive conformation of the essential D-Trp side chain in the somatostatin pharmacophore.

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Section: Resultsmentioning

confidence: 90%

Highly Potent 4-Amino-indolo[2,3-c]azepin-3-one-Containing Somatostatin Mimetics with a Range of sst Receptor Selectivities

et al. 2008

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“…In a recent work, natural amino acids were substituted with betidamino acids (monoacylated derivatives of a-aminoglycine) in order to develop an sst1 selective ligand [55]. The authors based their analog design on previous NMR analysis which was originally used for identification of the binding motif based on the 3D consensus structure [56]. In the same manner, in recent years, NMR analysis was performed on various analogs which are selective towards other sst receptors [57][58][59].…”

Section: The Need For Sst-selective Somatostatin Analogsmentioning

confidence: 99%

Improvement of drug-like properties of peptides: the somatostatin paradigm

Ovadia

Greenberg

Laufer

et al. 2010

Expert Opinion on Drug Discovery

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“…Systematic analysis of the effect of substitutions in the receptor sequence, combined with molecular modelling, is revealing the key residues responsible for receptor affinity and potency, duration of action and selectivity. Based on this information, precision peptide agonist and antagonist drugs with highly specific effects on subtypes of receptors for somatostatin and adrenocorticotropin-releasing hormone are being designed [for example, see [29]].…”

Section: Developing Drugsmentioning

confidence: 99%

Endocrine Receptors as Targets for New Drugs

Altman¹

2006

Neuroendocrinology

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Increasingly detailed knowledge of cellular signalling pathways is providing a sound basis for the development of specific drugs aimed at selected components of the pathways. Many of these targets are receptors and the multitude of hormone receptors makes endocrine functions a rich proving ground for this research. This article reviews a recent meeting (Insights into Receptor Function and New Drug Development Targets; 5th Endocrinology Colloquium of the Fondation Ipsen, Paris, December 5, 2005) where progress in defining suitable targets for drug therapies in the endocrine system and in designing drugs for some of these targets was discussed. Although the family of G-protein-coupled receptors, ubiquitous in the endocrine system, was the central focus, comparisons with other receptor families were made. Many mutations affecting genes coding for receptors or other components of signalling pathways have been found in a wide range of endocrine disorders including obesity, parathyroid malfunction, disorders involving thyroid-stimulating hormone and follicle-stimulating hormone, and tumours in the anterior pituitary, as well as in many types of cancer. These are being used to dissect the normal control mechanisms as well as to provide information for the development of selective drugs. Recently identified mutations that affect the intracellular traffic in newly synthesised receptors open up possibilities of another dimension of cellular regulation of signalling. Both the discovery of hormones such as apelin and its pairing with an ‘orphan’ receptor, and the unexpected action of a drug against cannabinoid receptors point to further levels of complexity in cardiovascular regulation. Deeper understanding of the evolution of receptor families and of the molecular mechanisms of signal transduction is enabling the design of highly specific agonists and antagonists. Pharmacological intervention is not limited to the ligand-receptor interaction but can extend to inhibition of selected steps in the intracellular pathway, such as the regulation of G protein deactivation. The progress in this area is both leading to improved treatment for a range of endocrine disorders and serving as a model for the study of signalling in other physiological systems.

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Somatostatin Receptor 1 Selective Analogues: 4. Three-Dimensional Consensus Structure by NMR

Cited by 29 publications

References 43 publications

Highly Potent 4-Amino-indolo[2,3-c]azepin-3-one-Containing Somatostatin Mimetics with a Range of sst Receptor Selectivities

Highly Potent 4-Amino-indolo[2,3-c]azepin-3-one-Containing Somatostatin Mimetics with a Range of sst Receptor Selectivities

Improvement of drug-like properties of peptides: the somatostatin paradigm

Endocrine Receptors as Targets for New Drugs

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