| Title | Synthesis and activities of cyclic thrombin receptor- derived peptide analogues of the Ser42-Phe-Leu-Leu-Arg46 motif sequence, containing 2,3-diaminopropionic acid | |
| Authors | Dimitris Panagiotopoulos1, Kostas Alexopoulos1, John M. Matsoukas1, Thomas Mavromoustakos2, Efthimia Theodoropoulou2, Evangelos Kalatzis2, Panayotis Fatseas3, Mahmoud Saifeddine4 and Morley D. Hollenberg4
1. Department of Chemistry, University of Patras, Patras 265 00, Greece 2. Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, Athens 116 35, Greece 3. 2n Department of Cardiology, Onassis Cardiac Surgery Center, 356 Sygrou Ave., 17674 Athens, Greece 4. Department of Pharmacology and Therapeutics, University of Calgary, Calgary Alberta, Canada R2N 4Nl |
|
| Citation | Panagiotopoulos, D., Alexopoulos, K., Matsoukas, J.M., Mavromoustakos, T., Theodoropoulou, E. et al.: Synthesis and activities of cyclic thrombin receptor- derived peptide analogues of the Ser42-Phe-Leu-Leu-Arg46 motif sequence, containing 2,3-diaminopropionic acid, Epitheorese Klin. Farmakol. Farmakokinet. 11(2-3): 128-131 (1997) | |
| Publication Date | 1997 | |
| Full Text Language | English | |
| Order – Buy | pharmakonpress[at]pharmakonpress[.]gr | |
| Keywords | SFLLR, synthesis, cyclic analogues. | |
| Other Terms | review article | |
| Summary | Cyclic analogues of the active Thrombin Receptor Peptide H-Ser-Phe-Leu-Leu-Arg-OH (TRP42-46) containing 2,3-diaminopropionic acid (Dap), Lys and L- or D-Phe have been prepared by the solid phase method. The pre-cyclic linear hexapeptides were synthesized using the acid sensitive 2-chlorotrityl (2-CLT) resin as solid support and cycilzation was achieved using 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate – (TBTU) as coupling reagent. Cyclization was achieved by forming an amide linkage between the -NH2 and -COOH groups of the two leucine residues located at the N- and C-terminal positions of the linear protected precursor H2N-Leu-Arg(Pmc)-εLys- Dap(Boc)Phe-Leu-OH (εLys denoting that the ε-amino group of Lys was coupled to the α-carboxyl of Arg). The identity of the compounds, after preparative reverse-phase HPLC purification, was confirmed by FAB MS and NMR methods. The cyclic analogues cyclo-(Phe-Leu-Leu-Arg-εLys-Dap) (1) and cyclo-(D-Phe-Leu-Leu-Arg- εLys-Dap) (2) were assessed for their contractile activity in a rat gastric longitudinal muscle (LM) bioassay system which has been used previously to evaluate the biological activities of linear thrombin receptor-derived polypeptides such as H-Ser-Phe-Leu-Leu-Arg-OH (P5) and HSer-Phe- Leu-Leu-Arg-NH2 (P5-NH2). Compound 1 exhibited higher contractile activity compared to compound 2 and compared to that of P5-NH2. These data are in line with previous suggestions (J. Med. Chem. 1996, in press; LIPS 1996, in press) that maximum activity is achieved through a combined interaction of the two pharmacophoric groups Phe/Arg and an adjacent free amino group. | |
| References | 1. Coughlin S.R., Vu T.K.H., Hung D.T, Wheaton V.I.: J. Clin, Invest. 89: 351 (1992)
2. Yang S.G., Laniyonu A.A., Saifeddine M., Moore G.J., Hollenberg M.D.: Life Sci. 51: 1325 (1992) 3. Hollenberg M.D., Yang S.G., Laniyonu A.A., Moore G.J., Saifeddine M.: Mol. Pharmacol. 42: 186 (1992) 4. Hollenberg M.D., Laniyonou A.A.. Saifeddine M., Moore G.J.: Mol. Pharmacol. 43: 921 (1993) 5. Chao B.H., Kalkunte S., Maraganore J.M., Stone S.R.: Biochemistry 31: 6175 (1992) 6. Vassalo R.R., Kieber-Emmons T., Cichowski K., Brass L.F.: J. Biol. Chem. 267: 6081 (1992) 7. Barlos K„ Gatos D., Hondrelis J., Matsoukas J.M., Moore G.J., Schafer W., Sotiriou P.: Liebigs Ann. Chem.: 951 (1989) 8. Matsoukas J.M., Hondrelis J., Agelis G., Barlos K., Gatos D., Ganter R„ Moore D., Moore, G.J.: J. Med, Chem. 37: 2958 (1994) 9. Panagiotopoulos D.( Matsoukas J.M., Kerarnida M., Gatos D., Monteiro L., Maia H.L.S., Yamdagni R., Wu Q., Redstone P., Moore G.J., Laniyonu A.A., Saifeddine M., Hoilen- berg M.D.: In: Peptides 1994 (Maia H.L.S., ed.), PP- 359-360, ESCOM, Leiden, 1995 10. Matsoukas J.M., Panagiotopoulos D.( Kerarnida M., Mavromoustakos T., Yamdagni R., Wu Q., Moore G J., Saifeddine M., Hollenberg M.D.: J. Med. Chem.: (1996) in press 11. Mavromoustakos T., Yang D.P., Theodoropoulou E.: Eur. J. Med. Chem. 30: 227 (1995) |
|
| Relative Papers |
Online ISSN 1011-6575
Άρθρα Δημοσιευμένα σε αυτό το Περιοδικό Καταχωρούνται στα:
- Chemical Abstracts
- Elsevier’s Bibliographic Databases: Scopus, EMBASE, EMBiology, Elsevier BIOBASE SCImago Journal and Country Rank Factor
Articles published in this Journal are Indexed or Abstracted in: • Chemical Abstracts • Elsevier’s Bibliographic Databases: Scopus, EMBASE, EMBiology, Elsevier BIOBASE SCImago Journal and Country Rank Factor
Συντακτικη Επιτροπή-Editorial Board