N-Methylated Sst2 Selective Somatostatin Cyclic Peptide Analogue As a Potent Candidate for Treating Neurogenic Inflammation

Overview

Journal ACS Med Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2014 Jun 6

PMID 24900340

Citations 3

Authors

Jayanta Chatterjee

Burkhardt Laufer

Johannes G Beck

Zsuzsanna Helyes

Erika Pinter

Janos Szolcsanyi

Aniko Horvath

Jozsef Mandl

Jean C Reubi

Gyorgy Keri

Horst Kessler

Affiliations

Soon will be listed here.

Abstract

A focused multiply N-methylated library of a cyclic hexapeptidic somatostatin analogue: MK678 cyclo(-MeAYwKVF-) was generated, which resulted in the unexpected observation of an efficacious tetra-N-methylated analogue, cyclo(-MeAYMewMeKVMeF-) with a potent inhibitory action on sensory neuropeptide release in vitro and on acute neurogenic inflammatory response in vivo. The analogue shows selectivity toward somatostatin receptor subtype 2 (sst2). Extensive 2D NMR spectroscopy and molecular dynamics simulation revealed the solution conformation of the analogue, which can be adopted as a lead for the further structure-activity relationship studies targeting neurogenic inflammation.

Citing Articles

Plasma Somatostatin Levels Increase during Scoliosis Surgery, but Not Herniated Disc Operations: Results of a Pilot Study.

Suto B, Kolumban B, Szabo E, Pasztor S, Nemeth T, Bagoly T Biomedicines. 2023; 11(8).

PMID: 37626651 PMC: 10452449. DOI: 10.3390/biomedicines11082154.

Insights into structure-activity relationships of somatostatin analogs containing mesitylalanine.

Martin-Gago P, Aragon E, Gomez-Caminals M, Fernandez-Carneado J, Ramon R, Martin-Malpartida P Molecules. 2013; 18(12):14564-84.

PMID: 24287991 PMC: 6270305. DOI: 10.3390/molecules181214564.

Synthesis of N-methylated cyclic peptides.

Chatterjee J, Laufer B, Kessler H Nat Protoc. 2012; 7(3):432-44.

PMID: 22322216 DOI: 10.1038/nprot.2011.450.

References

Helyes Z, Elekes K, Nemeth J, Pozsgai G, Sandor K, Kereskai L . Role of transient receptor potential vanilloid 1 receptors in endotoxin-induced airway inflammation in the mouse. Am J Physiol Lung Cell Mol Physiol. 2007; 292(5):L1173-81. DOI: 10.1152/ajplung.00406.2006. View

Reisine T, Bell G . Molecular properties of somatostatin receptors. Neuroscience. 1995; 67(4):777-90. DOI: 10.1016/0306-4522(95)00072-q. View

Helyes Z, Nemeth J, Pinter E, Szolcsanyi J . Inhibition by nociceptin of neurogenic inflammation and the release of SP and CGRP from sensory nerve terminals. Br J Pharmacol. 1997; 121(4):613-5. PMC: 1564754. DOI: 10.1038/sj.bjp.0701209. View

Ovadia O, Greenberg S, Laufer B, Gilon C, Hoffman A, Kessler H . Improvement of drug-like properties of peptides: the somatostatin paradigm. Expert Opin Drug Discov. 2012; 5(7):655-71. DOI: 10.1517/17460441.2010.493935. View

Szolcsanyi J, Pinter E, Helyes Z, Oroszi G, Nemeth J . Systemic anti-inflammatory effect induced by counter-irritation through a local release of somatostatin from nociceptors. Br J Pharmacol. 1998; 125(4):916-22. PMC: 1571027. DOI: 10.1038/sj.bjp.0702144. View

Chatterjee J, Ovadia O, Zahn G, Marinelli L, Hoffman A, Gilon C . Multiple N-methylation by a designed approach enhances receptor selectivity. J Med Chem. 2007; 50(24):5878-81. DOI: 10.1021/jm701044r. View

Bolcskei K, Helyes Z, Szabo A, Sandor K, Elekes K, Nemeth J . Investigation of the role of TRPV1 receptors in acute and chronic nociceptive processes using gene-deficient mice. Pain. 2005; 117(3):368-376. DOI: 10.1016/j.pain.2005.06.024. View

Yan L, Tatarek-Nossol M, Velkova A, Kazantzis A, Kapurniotu A . Design of a mimic of nonamyloidogenic and bioactive human islet amyloid polypeptide (IAPP) as nanomolar affinity inhibitor of IAPP cytotoxic fibrillogenesis. Proc Natl Acad Sci U S A. 2006; 103(7):2046-51. PMC: 1413694. DOI: 10.1073/pnas.0507471103. View

Veber D, SAPERSTEIN R, NUTT R, Freidinger R, Brady S, Curley P . A super active cyclic hexapeptide analog of somatostatin. Life Sci. 1984; 34(14):1371-8. DOI: 10.1016/0024-3205(84)90009-2. View

10.

Veber D, Freidlinger R, Perlow D, Paleveda Jr W, HOLLY F, STRACHAN R . A potent cyclic hexapeptide analogue of somatostatin. Nature. 1981; 292(5818):55-8. DOI: 10.1038/292055a0. View

11.

Maggi C . Tachykinins and calcitonin gene-related peptide (CGRP) as co-transmitters released from peripheral endings of sensory nerves. Prog Neurobiol. 1995; 45(1):1-98. DOI: 10.1016/0301-0082(94)e0017-b. View

12.

Chatterjee J, Gilon C, Hoffman A, Kessler H . N-methylation of peptides: a new perspective in medicinal chemistry. Acc Chem Res. 2008; 41(10):1331-42. DOI: 10.1021/ar8000603. View

13.

Biron E, Chatterjee J, Kessler H . Optimized selective N-methylation of peptides on solid support. J Pept Sci. 2005; 12(3):213-9. DOI: 10.1002/psc.711. View

14.

Szolcsanyi J, Helyes Z, Oroszi G, Nemeth J, Pinter E . Release of somatostatin and its role in the mediation of the anti-inflammatory effect induced by antidromic stimulation of sensory fibres of rat sciatic nerve. Br J Pharmacol. 1998; 123(5):936-42. PMC: 1565240. DOI: 10.1038/sj.bjp.0701685. View

15.

Biron E, Chatterjee J, Ovadia O, Langenegger D, Brueggen J, Hoyer D . Improving oral bioavailability of peptides by multiple N-methylation: somatostatin analogues. Angew Chem Int Ed Engl. 2008; 47(14):2595-9. DOI: 10.1002/anie.200705797. View

16.

Reubi J, Schar J, Waser B, Wenger S, Heppeler A, Schmitt J . Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur J Nucl Med. 2000; 27(3):273-82. DOI: 10.1007/s002590050034. View

17.

Scholzen T, Armstrong C, Bunnett N, Luger T, Olerud J, Ansel J . Neuropeptides in the skin: interactions between the neuroendocrine and the skin immune systems. Exp Dermatol. 1998; 7(2-3):81-96. DOI: 10.1111/j.1600-0625.1998.tb00307.x. View

18.

Pinter E, Helyes Z, Szolcsanyi J . Inhibitory effect of somatostatin on inflammation and nociception. Pharmacol Ther. 2006; 112(2):440-56. DOI: 10.1016/j.pharmthera.2006.04.010. View

19.

Chatterjee J, Mierke D, Kessler H . N-methylated cyclic pentaalanine peptides as template structures. J Am Chem Soc. 2006; 128(47):15164-72. DOI: 10.1021/ja063123d. View