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2004 | 51 | 1 | 51-56

Article title

Tryptic digestion of peptides corresponding to modified fragments of human growth hormone-releasing hormone.

Content

Title variants

Languages of publication

EN

Abstracts

EN
The objective of this study was to examine the degradation of short peptides corresponding to modified fragments of human growth hormone-releasing hormone by trypsin. Six analogues of pentapeptide 9-13 of human growth hormone-releasing hormone containing homoarginine, ornithine, glutamic acid, glycine, leucine or phenylalanine residue in position 11, two analogues of hexapeptide 8-13 of human growth hormone-releasing hormone and two analogues of heptapeptide 7-13 of human growth hormone-releasing hormone containing homoarginine or glycine residue in position 11 were obtained. The peptides were subjected to digestion by trypsin and the course of reaction was monitored using HPLC. It was found that the rate of hydrolysis of the Lys12-Val13 peptide bond depends on the amino-acid residue preceding Lys12. The extension of the peptide chain towards the N-terminus by introduction of consecutive amino-acid residues corresponding to the human growth hormone-releasing hormone sequence accelerates the hydrolysis process. These results may be of assistance in designing new analogues of human growth hormone-releasing hormone, more resistant to the activity of proteolytic enzymes.

Year

Volume

51

Issue

1

Pages

51-56

Physical description

Dates

published
2004
received
2003-10-31
revised
2004-02-04
accepted
2004-02-08

Contributors

author
  • Laboratory of Peptides, Faculty of Chemistry, Warsaw University, L. Pasteura 1, 02-093 Warszawa, Poland
  • Laboratory of Peptides, Faculty of Chemistry, Warsaw University, L. Pasteura 1, 02-093 Warszawa, Poland
author
  • Laboratory of Peptides, Faculty of Chemistry, Warsaw University, L. Pasteura 1, 02-093 Warszawa, Poland

References

  • Campbell RM, Striker P, Bongers J, Liu W, Lambros T, Ahmad M, Felix AM, Heimer EP. (1994) Enhanced stability and potency of novel growth hormone-releasing factor (GRF) analogues derived from rodent and human GRF sequences. Peptides.; 15: 489-95.
  • Frohman LA, Downs TR, Williams TC, Heimer EP, Pan Y-CE, Felix AM. (1986) Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to biologically inactive product cleaved at the NH2 terminus. J Clin Invest.; 78: 906-13.
  • Frohman LA, Downs TR, Heimer EP, Felix AM. (1989) Dipeptidylpeptidase IV and trypsin-like enzymatic degradation of human growth hormone-releasing hormone in plasma. J Clin Invest.; 83: 1533-40.
  • Gelato MC, Ross JL, Malozowski S, Pescovitz OH, Skeda M, Loriaux DL, Merriam GR. (1985) Effects of pulsatile administration of growth hormone (GH)-releasing hormone on short term linear growth in children with GH deficiency. J Clin Endocrinol Metab.; 61: 444-450.
  • Izdebski J, Pinski J, Horvath JE, Halmos G, Groot K, Schally AV. (1995) Synthesis and biological evaluation of superactive agonists of growth hormone-releasing hormone. Proc Natl Acad Sci USA.; 92: 4872-6.
  • Izdebski J, Witkowska E, Kunce D, Orłowska A, Baranowska B, Radzikowska M, Smoluch M. (2002) New potent hGH-RH analogues with increased resistance to enzymatic degradation. J Pept Sci.; 8: 289-96.
  • Kubiak TM, Friedman AR, Martin RA, Ichhpureni AK, Alaniz GR, Clafin WH, Goodwin MC, Cleary DL, Kelly CR, Hilman RM, Downs TR, Frohman LA, Mosely WM. (1993) Position 2 and position 2/Ala15-substituted analogues of bovine growth hormone- releasing factor (bGRF) with enhanced metabolic stability and improved in vivo bioactivity. J Med Chem.; 36: 888-97.
  • Lance VA, Murphy WA, Sueiras-Diaz J, Coy D. (1984) Superactive analogs of growth hormone-releasing factor(1-29)-amide. Biochem Biophys Res Commun.; 119: 265-72.
  • Ross RJM, Tsagarakis S, Grossman A, Preece MA, Rodda C, Davis PSW, Rees LH, Savage MO. (1987) Treatment of growth-hormone deficiency with growth-hormone-releasing hormone. Lancet.; i: 5-8.
  • Thorner MO, Reschke J, Chitwood J, Rogol AD, Furlanetto R, Rivier J, Vale W, Blizzard RM. (1985) Acceleration of growth in two children treated with human growth hormone-releasing factor. N Engl J Med.; 312: 4-9.
  • Wehrenberg WB, Ling N. (1983) In vivo biological potency of rat and human growth hormone-releasing factor and fragments of human growth hormone-releasing factor. Biochem Biophys Res Commun.; 115: 525-30.
  • Witkowska E, Orłowska A, Sagan B, Smoluch M, Izdebski J. (2001) Tryptic hydrolysis of hGH-RH(1-29)-NH2 analogues containing Lys or Orn in position 12 and 21. J Pept Sci.; 7: 166-72.

Document Type

Publication order reference

Identifiers

YADDA identifier

bwmeta1.element.bwnjournal-article-abpv51i1p51kz
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