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2004 | 51 | 1 |

Tytuł artykułu

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

Warianty tytułu

Języki publikacji

EN

Abstrakty

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.

Wydawca

-

Rocznik

Tom

51

Numer

1

Opis fizyczny

p.51-56,ref.

Twórcy

autor
  • Warsaw University, L.Pasteura 1, 02-093 Warsaw, Poland
autor
autor

Bibliografia

  • 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, Orlowska A, Baranowska B, Radzikowska M, Smoluch M. (2002) New potent hGH- RH analogues with increased resistance to enzymatic degradation. JPept 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 Mied 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, Orlowska 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.

Typ dokumentu

Bibliografia

Identyfikatory

Identyfikator YADDA

bwmeta1.element.agro-article-23418046-c01b-4bd6-a54e-605f6b079fdd
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