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Octapeptide Analogs of Somatostatin Containing α,α-Dialkylated Amino Acids with Potent Anticancer Activity

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We describe the synthesis and anticancer activities of octapeptide analogs of somatostatin incorporating α,α-dialkylated amino acids. The designed analogs of somatostatin are: d-Phe1-Cys2-Tyr3-d-Trp4-Orn5-Xxx6-Pen7-Thr8-NH2 where Xxx=α-Aminoisobutyric acid (Aib), Diethyl glycine (Deg), 1-Aminocyclopentane carboxylic acid (Ac5c), and, d-Phe1-Cys2-Tyr3-d-Trp4-Lys5-Ac5c6-Pen7-Thr8-NH2 (disulphide bond between Cys2 and Pen7 in all analogs). The conformational studies two of the designed analogs were carried out by NMR techniques and the experimental results suggest a β-turn structure for one of the designed analog. In vivo tumor regression study of two designed analogs on human primary colon tumor xenografts in nude mice demonstrates the anticancer potential of the synthesized analogs.

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Abbreviations

Orn:

Ornithine

Pen:

Penicillamine

Aib:

α-Aminoisobutyric acid

Deg:

α,α-Di-ethylglycine

Ac5c:

1-Aminocyclopentane carboxylic acid

References

  • Bauer W., Briner U., Doepfner W., Haller R., Huguenin R., Marbach P., Petcher T. J., Pless M.. (1982) Life Sci 31:1133–1140

    Article  PubMed  CAS  Google Scholar 

  • Cai R. Z., Karashima T., Guoth J., Szoke B., Olsen D., Schally A. V., (1987) Proc. Natl. Acad. Sci. USA 84:2502–2506

    Article  PubMed  CAS  Google Scholar 

  • Cai R. Z., Szoke B., Lu R., Fu D., Redding T. W., Schally A. V. (1986). Proc. Natl. Acad. Sci. USA 83:1896–1900

    Article  PubMed  CAS  Google Scholar 

  • Capello A., Krenning E. P., Bernard B. F., Breeman W. A., van Hagen M. P., de Jong M., (2004) J. Nucl. Med 45:1716–1720

    PubMed  CAS  Google Scholar 

  • Dasgupta P., Singh A., Mukherjee R., (2002) Biol. Pharm. Bull 25:29–36

    Article  PubMed  CAS  Google Scholar 

  • Grimberg A., (2004) Cancer Biol. Ther 3:731–733

    Article  PubMed  CAS  Google Scholar 

  • Hruby V. J., (1985) Trends Pharm. Sci 6:259–262

    Article  CAS  Google Scholar 

  • Janecka A., Zubrzycka M., Janecki T., (2001) J. Pept. Res 58:91–107

    Article  PubMed  CAS  Google Scholar 

  • Karle I. L., Balaram P., (1990) Biochemistry 29:6747–6756

    Article  PubMed  CAS  Google Scholar 

  • Karle I. L., Rao R. B., Prasad S., Kaul R., Balaram P., (1994) J. Amer. Chem. Soc 116:10335–10361

    Article  Google Scholar 

  • Karle I. L., Gurunath R., Prasad S., Kaul R., Rao R.B., Balaram P. (1995) J. Amer. Chem. Soc 117:9632–9637

    Article  CAS  Google Scholar 

  • Kazmierski W. M., Ferguson R. D., Lipkowski A. W., Hruby V. J., (1995) Int. J. Pept. Protein Res 46:265–278

    Article  PubMed  CAS  Google Scholar 

  • Lamberts S. W. J., de Herder W. W., Hofland L. J., (2002) Trends Endocrinol. Metab 13:451–457

    Article  PubMed  CAS  Google Scholar 

  • Mattern R. H., Tran T. A., Goodman M., (1999) J. Pept. Res 53:146–160

    Article  PubMed  CAS  Google Scholar 

  • Mukherjee, R. and Jaggi, M.: 2000. Drug for the treatment of cancer US Patent 6,156,725

  • Murphy W. A., Heiman M. L., Lance V. A., Mezo I., Coy D. H., (1985) Biochem. Biophys. Res. Commun 132:922–928

    Article  PubMed  CAS  Google Scholar 

  • Pelton J. T., Whalon M., Cody W. L., Hruby V. J., (1988) Int. J. Pept. Protein Res 31:109–115

    Article  PubMed  CAS  Google Scholar 

  • Pless M., Waldherr C., Maecke H., Buitrago C., Herrmann R., Mueller-Brand J., (2004) Lung Cancer 45:365–371

    Article  PubMed  Google Scholar 

  • Prasad S., BalajiRao R., Bergsstand H., Lindquist B., Becker E. L., Balaram P (1996) Int. J. Pept. Protein Res 48:312–318

    Article  PubMed  CAS  Google Scholar 

  • Prasad S., Rao R. B., Balaram P., (1995) Biopolymers 35:11–20

    Article  PubMed  CAS  Google Scholar 

  • Scarpignato C., Pelosini I., (2001) Chemotherapy 47:1–29

    Article  PubMed  CAS  Google Scholar 

  • Schally A. V., Szepeshazi K., Nagy A., Comaru-Schally A. M., Halmos G., (2004) Cell Mol. Life Sci 61:1042–1068

    Article  PubMed  CAS  Google Scholar 

  • Schmitt A., Bernhardt P., Nilsson O., Ahlman H., Kolby L., Maecke H. R., Forssell-Aronsson E., (2004) J. Nucl. Med 45:1542–1548

    PubMed  CAS  Google Scholar 

  • Toniolo C., Crisma M., Valle G., Bonora G. M., Polinelli S., Becker E. L., Freer R. J., Prasad S., Rao R. B., Balaram P., (1989) Peptide Res 2:275–281

    CAS  Google Scholar 

  • Tran T. A., Mattern R. H., Morgan B. A., Taylor J. E., Goodman M., (1999) J. Peptide Res 53:134–145

    Article  CAS  Google Scholar 

  • Veber D. F., Freidlinger R. M., Perlow D. S., Paleveda W. J. Jr., Holly F. W., Strachan R. G., Nutt R. F., Arison B. H., Homnick C., Randall W. C., Glitzer M. S., Saperstein R., Hirschmann R., (1981) Nature 292:55–58

    Article  PubMed  CAS  Google Scholar 

  • Veber D. F., Saperstein R., Nutt R. F., Freidinger R. M., Brady S. F., Curley P., Perlow D. S., Paleveda W. J., Colton C. D., Zacchei A. G., (1984) Life Sci 34:1371–1378

    Article  PubMed  CAS  Google Scholar 

  • Weckbecker G., Lewis I., Albert R., Schmid H. A., Hoyer D., Bruns C., (2003) Nat. Rev. Drug Discov 12:999–1017

    Article  CAS  Google Scholar 

  • Zatelli M. C., Piccin D., Bottoni A., Ambrosio M. R., Margutti A., Padovani R., Scanarini M., Taylor J. E., Culler M. D., Cavazzini L., degli Uberti E. C., (2004) J. Clin. Endocrinol. Metab 89:5181–5188

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We are thankful to Dr. Anand C. Burman, Chairman, Dabur Research Foundation for financial support.

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Authors and Affiliations

  1. Dabur Research Foundation, 22, Site IV, Sahibabad, 201010, Ghaziabad, Uttar Pradesh, India

    Sudhanand Prasad (Dr.), Archna Mathur, Rajan Sharma, Neena Gupta, Rinku Ahuja, Manu Jaggi, Anu T. Singh & Rama Mukherjee

  2. New Drug Research, Dabur Research Foundation, 22, Site IV, Sahibabad, 201010, Ghaziabad, Uttar Pradesh, India

    Sudhanand Prasad (Dr.)

Authors
  1. Sudhanand Prasad
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  2. Archna Mathur
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  3. Rajan Sharma
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  4. Neena Gupta
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  5. Rinku Ahuja
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  6. Manu Jaggi
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  7. Anu T. Singh
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  8. Rama Mukherjee
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Correspondence to Sudhanand Prasad.

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Prasad, S., Mathur, A., Sharma, R. et al. Octapeptide Analogs of Somatostatin Containing α,α-Dialkylated Amino Acids with Potent Anticancer Activity. Int J Pept Res Ther 12, 179–185 (2006). https://doi.org/10.1007/s10989-005-9005-0

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  • DOI: https://doi.org/10.1007/s10989-005-9005-0

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