Abstract
Synthesis of the first phosphorus (V) porphyrin-peptide conjugate was successfully accomplished. A biologically active peptide, leucine enkephalin, was constructed on the phosphorus atom of the 5,10,15,20-meso-tetraphenylporphinato dichlorophosphorus (V) chloride. The method involved solution phase peptide synthesis. The first C-terminal amino acid in the sequence of the peptide was axially attached to the porphyrin through a linker, 3-aminopropanol, and the remainder of leucine enkephalin was synthesized by subsequent additions of amino acids. Leucine enkephalin-P(V) porphyrin conjugate represents a new group of compounds, and its synthesis broadens potential applications of P(V) porphyrine, e.g. in photodynamic therapy.
[1] H. Li and L. Czuchajowski: “Synthesis and biomedical application of porphyrinyl nucleosides, nucleotides and oligonucleotides”, Trends in Heterocyclic Chemistry, Vol. 6, (1999), pp. 57–77, and the references therein. Search in Google Scholar
[2] X. Wang, O.S. Fedorova, W.R. Trumble and L. Czuchajowski: “Porphyrin-psoralen conjugate as a new DNA ligand”, Russian Journal of Bioorganic Chemistry, Vol. 25, No. 3, (1999), pp. 220–225. Search in Google Scholar
[3] K.-M. Goh and L. Czuchajowski: “The synthesis of isomeric dithymidyl-phosphorus (V)-meso-tetraphenylporphyrins”, Journal of Porphyrins and Phthalocyanines, Vol. 1, No. 3, (1997), pp. 281–285. http://dx.doi.org/10.1002/(SICI)1099-1409(199707)1:3<281::AID-JPP32>3.0.CO;2-L10.1002/(SICI)1099-1409(199707)1:3<281::AID-JPP32>3.0.CO;2-LSearch in Google Scholar
[4] H. Segawa, K. Kunimoto A. Nakamoto and T. Shimidzu: “Synthesis of axial dialkoxy phosphorus (V) porphyrin derivatives. Novel hypervalent phosphorus compounds”, J. Chem. Soc., Perkin Trans., Vol. 1, No. 8, (1992), pp. 939–940. http://dx.doi.org/10.1039/p1992000093910.1039/P19920000939Search in Google Scholar
[5] M. Kitamura, A. Nimura, K. Kumimoto, H. Segawa and T. Shimidzu: “Synthesis and properties of oligonucleotide derivative with P(V) porphyrin”, Nucleic Acid Res., Symp., Vol. 25 (1991), pp. 13–14. Search in Google Scholar
[6] H. Segawa, N. Nakayama and T. Shimidzu: “Electrochemical synthesis of one-dimensional donor-acceptor polymers containing oligothiophenes and phosphorus porphyrins”, J. Chem. Soc., Chem. Commun., (1992), pp. 784–786. Search in Google Scholar
[7] H. Segawa, A. Nakamoto and T. Shimidzu: “Photoinduced axial bond exchange reaction of dichlorophosphorus (V) tetraphenylporphyrin chloride: photochemical activation of central three-centre four-electron bond through the s-p interaction”, J. Chem. Soc., Chem. Commun., (1992), pp. 1066–1067. Search in Google Scholar
[8] K. Kunimoto, H. Segawa and T. Shimidzu: “Selective synthesis of unsymmetrical dialkoxyphosphorus (V) tetraphenylporphine derivatives by stepwise substitution of axial position”, Tetrahedron Lett., Vol. 33 (1992), pp. 6327–6330. http://dx.doi.org/10.1016/S0040-4039(00)60965-610.1016/S0040-4039(00)60965-6Search in Google Scholar
[9] B.G. Maiya and R.D. Reddy: “A molecular photo-switch based on an ‘axial-bonding’ type phosphorus (V) porphyrin”, Chem. Commun., (2001), pp. 117–118. Search in Google Scholar
[10] M. Comb, P.H. Seeburg, J. Adelman, L. Eiden and E. Herbert: “Primary structure of the human Met- and Leu-enkephalin precursor and its mRNA”, Nature, Vol. 295, (1982), pp. 663–667. http://dx.doi.org/10.1038/295663a010.1038/295663a0Search in Google Scholar
[11] J. Hughes, T.W. Smith, H.W. Kosterlitz, L.A. Fothergill, B.A. Morgan and H.R. Morris: “Identification of two related pentapeptides from the brain with potent opiate agonist activity”, Nature, Vol. 258, (1975), pp. 577–579. http://dx.doi.org/10.1038/258577a010.1038/258577a0Search in Google Scholar
[12] N. Sewald and H.-D. Jakubke: Peptides: Chemistry and Biology, Wiley-VCH, 2002, Chapter 3. 10.1002/352760068XSearch in Google Scholar
[13] B.M. Cox: “Endogenous opioid peptides: A guide to structures and terminology”, Life Sciences, Vol. 31, (1982), pp. 1645–1658. http://dx.doi.org/10.1016/0024-3205(82)90179-510.1016/0024-3205(82)90179-5Search in Google Scholar
[14] C.J. Carrano and M. Tsutsui: “Unusual metalloporphyrins. Phosphorus complexes of tetraphenylporphine”, J. Coord. Chem., Vol. 7, (1977) pp. 79–83. Search in Google Scholar
[15] M. anteunis and Ch. Becu: “Trimethylsilyl cyanide, a reagent and (co)solvent ‘par excellence’ for homogeneous peptide synthesis. A strategy circumventing classical drawbacks? Part 1”, Bull. Soc. Chim. Belg., Vol. 96, No. 2, (1987), pp. 119–130. http://dx.doi.org/10.1002/bscb.1987096020710.1002/bscb.19870960207Search in Google Scholar
[16] M.P. Gajewski and L. Czuchajowski: “p-Nitrobenzamide substituted phosphorus (V) porphyrins: synthesis and interactions with DNA”, submitted to Journal of Porphyrins and Phthalocyanines, (2004). Search in Google Scholar
[17] M.P. Gajewski and L. Czuchajowski: “Axially substituted phosphorus (V) porphyrins as analogues of meso-derivatized free base porphyrins”, submitted to Journal of Porphyrins and Phthalocyanines, (2004). Search in Google Scholar
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