Abstract
Studies in our laboratory have been directed towards understanding the mechanism of action of two hydrophobic toxins, pardaxin comprising 33 residues and δ-toxin comprising 26 residues. Since isolation of these peptides in large amounts from natural sources is not convenient, we have explored synthetic approaches to get these peptides as well as their analogs. We have used chemistry specific to fluorenylmethoxycarbonyl (Fmoc) andt-butyloxycarbonyl (Boc) amino acids. Synthesis specific for Fmoc amino acids was carried out manually as well as on a semi-automated continuous flow peptide synthesizer. Synthesis specific for Boc amino acids was carried out manually. The protocols used by us have yielded 15–33 residue peptides which are of high purity. Even in peptides where heterogeneity was present, pure peptide could be obtained in good yields using simple gradients in fast performance liquid chromatography. The synthesis of pardaxin, δ-toxin and several analogs should help in identifying the molecular determinants of biological activity.
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References
Atherton E and Sheppard R C 1989Solid phase peptide synthesis. A practical approach (Oxford: IRL)
Bernheimer A W and Rudy B 1986Biochem. Biophys. Acta 864 123
Bevins C L and Zasloff M 1990Annu. Rev. Biochem. 59 395
Boman H G 1991Cell 65 205
Clark-Lewis I, Acbersold R, Zillener H, Schader J W, Hood L E and Kent S B H 1986Science 235 134
Finn F M and Hofmann K 1976 InThe proteins (eds) H Neurath and R L Hill (New York: Academic Press) vol. 11, pp. 106–253
Fitton J E, Dell A and Shaw W V 1980FEBS Lett. 115 209
Galpin I J, Hancock F E, Handa B K, Jackson A G, Kenner G W, McDowell P, Nobel P and Ramage R 1981Tetrahedron 37 3043
Gisin B F 1973Helv. Chem. Acta 56 1476
Itoh M, Hagiwara D and Kaniya T 1975Tetrahedron Lett. 49 4393
Lehrer R I, Ganz T and Selsted M 1991Cell 64 229
Meienhofer J, Waki M, Heimer E P, Lambross T J, Makofske R C and Chang C D 1979Int. J. Peptide Protein Res. 13 35
Merrifield R B 1986Science 232 341
Milton R C de L, Milton S C F and Kent S B H 1992Science 256 1445
Reddy G L, Bikshapathy E and Nagaraj R 1985Tetrahedron Lett. 26 4257
Reddy G L and Nagaraj R 1986Proc. Indian Acad. Sci. (Chem. Sci.) 97 71
Saberwal G and Nagaraj R 1994Biochim. Biophys. Acta 1197 109
Stewart J M and Young D 1984 InSolid-phase synthesis 2nd edn (Pierce Chemical Co.: USA)
Taylor J W and Kaiser E T 1987Methods Enzymol. 154 473
Thompson S A, Tachibana K, Nakanishi K and Kubota I 1986Science 233 341
Wetzel R and Goeddel D V 1983 InThe Peptides: analysis, synthesis, biology (eds) E Gross and J Meienhofer (New York: Academic Press) vol. 5, pp. 2–64
Wlodawer A, Miller M, Jskolski M, Sathyanarayana B K, Baldurin E, Weber I T, Selk L M, Clawson L, Schneider J and Kent S B H 1989Science 245 616
Yajima H and Fujii N 1981J. Am. Chem. Soc. 103 5867
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Saberwal, G., Thennarasu, S., Dhople, V.M. et al. Studies on the synthesis of the toxins, pardaxin, δ-toxin and their analogues by solid-phase methods. Proc. Indian Acad. Sci. (Chem. Sci.) 106, 1109–1121 (1994). https://doi.org/10.1007/BF02841919
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DOI: https://doi.org/10.1007/BF02841919