Advertisement

Guide for Studies on Structure and Function Employing Synthetic Polypeptides

  • Emil T. Kaiser

Abstract

The systematic design of protein tertiary structure poses a formidable challenge in protein engineering. Several years ago we undertook the design of models for those peptides and proteins for which to a first approximation tertiary structure can be neglected (Kroon et al., 1978; Kaiser and Kezdy, 1983, 1984). Although the prediction of tertiary structure from primary sequence cannot as yet be made with confidence, it was our thesis that secondary structures could be built in a rational fashion. Furthermore, the reasonable hypothesis was proposed that in amphiphilic environments like that of a biological interface, complementary amphiphilic secondary structures (secondary structures having distinct hydrophobic and hydro- philic faces) may be induced in peptides and proteins binding on such interfaces. Therefore, as our initial objective we engaged in the modeling of peptides and proteins that have affinity for membranes.

Keywords

Peptide Hormone Salmon Calcitonin Model Peptide Helix Axis Human Calcitonin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Blanc, J. P., and Kaiser, E. T., 1984, Biological and physical properties of a ß-endorphin analog containing only D-amino acids in the amphiphilic helical segment 13-31, J. Biol. Chem. 259:9549–9556.PubMedGoogle Scholar
  2. Blanc, J. P., Taylor, J. W., and Kaiser, E. T., 1983, Examination of the requirement for an amphiphilic helical structure in ß-endorphin through the design, synthesis and study of model peptides, J. Biol. Chem. 258: 8277–8284.PubMedGoogle Scholar
  3. Brack, A., and Orgel, L. E., 1975, ß-Structures of alternating polypeptides and their possible prebiotic significance, Nature 256:383–387.PubMedCrossRefGoogle Scholar
  4. Briggs, M. S., and Gierasch, L. M., 1984, Exploring the conformational roles of signal sequences: Synthesis and conformation analysis of receptor protein wild-type and mutant signal peptides, Biochemistry 23:3111–3114.PubMedCrossRefGoogle Scholar
  5. Briggs, M. S., Cornell, D. G., Dluhy, R. A., and Gierasch, L. M., 1986, Spectroscopic studies of signal peptides in phospholipid monolayers: Conformations induced by lipids suggest possible initial steps in protein export, Science 233:206–208.PubMedCrossRefGoogle Scholar
  6. Chou, P. Y., and Fasman, G. D., 1978, Empirical predictions of protein conformation, Annu. Rev. Biochem. 47:251–276.PubMedCrossRefGoogle Scholar
  7. DeGrado, W. F., Kézdy, F. J., and Kaiser, E. T., 1981, Design, synthesis and characterization of a cytotoxic peptide with melittin-like activity, J. Am. Chem. Soc. 103:679–681.CrossRefGoogle Scholar
  8. Edelstein, C. Kézdy, F. J., Scanu, A. M., and Shen, B. W., 1979, Apolipoproteins and the structural organization of plasma lipoproteins: Human plasma high density lipoprotein-3, J. Lipid Res. 20:143–153.PubMedGoogle Scholar
  9. Emr, S. D., and Silhavy, T. J., 1983, Importance of secondary structure in the signal sequence for protein secretion, Proc. Natl. Acad. Sci. U.S.A. 80:4599–4603.PubMedCrossRefGoogle Scholar
  10. Engelman, D. M., and Steitz, T. A., 1981, The spontaneous insertion of proteins into and across membranes. The helical hairpin hypothesis, Cell 23:411–422.PubMedCrossRefGoogle Scholar
  11. Fitch, W. M., 1977, Phylogenies constrained by the crossover process as illustrated by human hemoglobins and a thirteen cycle, eleven amino acid repeat in human apolipoprotein A-I, Genetics 86:623–644.PubMedGoogle Scholar
  12. Fukushima, D., Kupferberg, J. P., Yokoyama, D., Kroon, D., Kaiser, E. T., and Kézdy, F. J., 1979, A synthetic amphiphilic helical docosapeptide with the surface properties of plasma apolipoprotein A-I, J. Am. Chem. Soc. 101:3703–3704.CrossRefGoogle Scholar
  13. Fukushima, D., Kaiser, E. T., Kézdy, F. J., Kroon, D. J., Kupferberg, J. P., and Yokoyama, S., 1980a, Rational design of synthetic models for lipoproteins, Ann. N.Y. Acad. Sci. 348:365–373.CrossRefGoogle Scholar
  14. Fukushima, D., Yokoyama, S., Kroon, D. J., Kezdy, F. J., and Kaiser, E. T., 1980b, Chain length-function correlation of amphiphilic peptides, J. Biol. Chem. 255:10651–10657.PubMedGoogle Scholar
  15. Fukushima, D., Yokoyama, S., Kezdy, F. J., and Kaiser, E. T., 1981, Binding of amphiphilic peptides to phospholipid/cholesterol unilamellar vesicles: A model for protein-cholesterol interactions, Proc. Natl. Acad. Sci. U.S.A. 78:2732–2736.PubMedCrossRefGoogle Scholar
  16. Green, F. R., Lynch, B., and Kaiser, E. T., 1987, Biological and physical properties of a model calcitonin containing a glutamate residue interrupting the hydrophobic face of the idealized amphiphilic α-helical region, Proc. Natl. Acad. Sci. U.S.A. 84:8340–8344.PubMedCrossRefGoogle Scholar
  17. Itoh, K., Foxman, B. M., and Fasman, G. D., 1976, The two ß-forms of polY(L-GLUTAMIC ACID), Biopolymers 15:419–455.PubMedCrossRefGoogle Scholar
  18. Kaiser, E. T., and Kezdy, F. J., 1983, Secondary structures of proteins and peptide in amphiphilic environments (a review), Proc. Natl. Acad. Sci. U.S.A. 80:1137–1143.PubMedCrossRefGoogle Scholar
  19. Kaiser, E. T., and Kezdy, F. J., 1984, Amphiphilic secondary structure: Design of peptide hormones, Science 223:249–255.PubMedCrossRefGoogle Scholar
  20. Kaiser, E. T., and Kezdy, F. J., 1987, Peptides with affinity for membranes, Annu. Rev. Biophys. Biophys. Chem. 16:561–581.PubMedCrossRefGoogle Scholar
  21. Kaiser, E. T., Lynch, B., and Rajashekhar, B., 1985, The design and construction of peptides and proteins with amphiphilic secondary structures, in: Proceedings 9th Annual Peptide Symposium, Toronto, Pierce Chemical Co., Rockford, IL, p. 855–864.Google Scholar
  22. Kendall, D. A., Bock, S. C., and Kaiser, E. T., 1986, Idealization of the hydrophobic segment of the alkaline phosphatase signal peptide, Nature 321:706–708.PubMedCrossRefGoogle Scholar
  23. Knott, T. J., Pease, R. J., Powell, L. M., Wallis, S. C., Rall, S. C., Jr., Innearity, T. L., Blackhart, B., Taylor, W. H., Marcel, Y., Milne, R., Johnson, D., Fuller, M., Lusis, A. J., McCarthy, B. J., Mahley, R. W., Levy-Wilson, B., and Scott, J., 1986, Complete protein sequence and identification of structural domains of human apolipoprotein B, Nature 323:734–738.PubMedCrossRefGoogle Scholar
  24. Kroon, D. J., Kupferberg, J. P., Kaiser, E. T., and Kezdy, F. J., 1978, Mechanism of lipid-protein interactions in lipoproteins. A synthetic peptide-lecithin vesicle model system, J. Am. Chem. Soc. 100:5975–5977.CrossRefGoogle Scholar
  25. Maier, R., Kamber, B., Riniker, B., and Rittel, W., 1976, Analogs of human calcitonin IV. Influence of leucine substitutions in positions 12, 16 and 19 on hypocalcemic activity in the rat, Clin. Endocrinol. 5: 327s–332s.CrossRefGoogle Scholar
  26. McLachlan, A. D., 1977, Repeated helical pattern in apolipoprotein A-I, Nature 267:465–466.PubMedCrossRefGoogle Scholar
  27. Moe, G. R., and Kaiser, E. T., 1985, Design, synthesis and characterization of a model peptide having potent calcitonin-like biological activity: Implications for calcitonin structure/activity, Biochemistry 24:1971–1976.PubMedCrossRefGoogle Scholar
  28. Moe, G. R., Miller, R. J., and Kaiser, E. T., 1983, Design ofa peptide hormone: Synthesis and characterization of a model peptide with calcitonin-like activity, J. Am. Chem. Soc. 105:4100–4102.CrossRefGoogle Scholar
  29. Nakagawa, S. H., Lau, H. S. H., Kezdy, F. J., and Kaiser, E. T., 1985, The use of polymer-bound oxime for the synthesis of large peptides usable in segment condensation: Synthesis of a 44 amino acid amphiphilic peptide model of apolipoprotein A-I, J. Am. Chem. Soc. 107:7087–7092.CrossRefGoogle Scholar
  30. Nakamuta, H., Furukawa, S., Koida, M., Yajima, H., Orlowski, R. C., and Schleuter, R., 1981, Specific binding of 125I-salmon calcitonin to rat brain: Regional variation and calcitonin specificity, Jpn. J. Pharmacal. 31:53–60.CrossRefGoogle Scholar
  31. Osterman, D., Mora, R., Kezdy, F. J., Kaiser, E. T., and Meredith, S., 1984, A synthetic amphiphilic ß-strand tridecapeptide: A model for apolipoprotein B, J. Am. Chem. Soc. 106:6845–6847.CrossRefGoogle Scholar
  32. Rajashekhar, B., and Kaiser, E. T., 1986, Design of biologically active peptides with non-peptidic structural elements: Biological and physical properties of a synthetic analogue of ß-endorphin with unnatural amino acids in the region 6-12, J. Biol. Chem. 261:13617–13623.PubMedGoogle Scholar
  33. Retzinger, G. S., Meredith, S. C., Lau, S. H., Kaiser, E. T., and Kezdy, F. J., 1985, A method for probing the affinity of peptides for amphiphilic surfaces, Anal. Biochem. 150:131–140.PubMedCrossRefGoogle Scholar
  34. Reynolds, J. A., 1980, Binding studies with apolipoproteins, Ann. N.Y. Acad. Sci. 348:174–183.PubMedCrossRefGoogle Scholar
  35. Rippon, W. B., Chen, H. H., and Walton, A. G., 1973, Spectroscopic characterization of poly(Glu-Ala), J. Mol. Biol. 75:369–375.PubMedCrossRefGoogle Scholar
  36. Rosenblatt, M., Beaudette, N. V., and Fasman, G. D., 1980, Conformation studies of the synthetic precursor-specific region of preproparathyroid hormone, Proc. Natl. Acad. Sci. U.S.A. 77:3983–3987.PubMedCrossRefGoogle Scholar
  37. Schiffer, M., and Edmundson, A. B., 1967, Use of helical wheels to represent the structures of proteins and to identify segments with helical potential, Biophys. J. 7:121–135.PubMedCrossRefGoogle Scholar
  38. Schröder, E., Lubke, K., Lehmann, M., and Beetz, I., 1971, Hemolytic activity and action on the surface tension of aqueous solutions of synthetic melittins and their derivatives, Experentia 26:764–768.Google Scholar
  39. Segrest, J. P., Jackson, R. L., Morrisett, J. D., and Gotto, A. M., Jr., 1974, A molecular theory of lipid-protein interactions in the plasma lipoproteins, FEBS Lett. 38:247–253.PubMedCrossRefGoogle Scholar
  40. Shinnar, A. E., and Kaiser, E. T., 1984, Physical and conformation properties of a synthetic leader peptide from M13 coat protein, J. Am. Chem. Soc. 106:5006–5007.CrossRefGoogle Scholar
  41. Taylor, J. W., and Kaiser, E. T., 1986, The structural characterization of ß-endorphin and related peptide hormones and neurotransmitters, Pharmacal. Rev. 38:291–319.Google Scholar
  42. Taylor, J. W., Osterman, D. G., Miller, R. J., and Kaiser, E. T., 1981, Design and synthesis ofa model peptide with ß-endorphin-like properties, J. Am. Chem. Soc. 103:6965–6966.CrossRefGoogle Scholar
  43. Taylor, J. W., Miller, R. J., and Kaiser, E. T., 1982, Structural characterization of ß-endorphin through the design, synthesis and study of model peptides, Mol. Pharmacal. 22:657–666.Google Scholar
  44. Taylor, J. W., Miller, R. J., and Kaiser, E. T., 1983, Characterization of an amphiphilic helical structure in ß-endorphin through the design, synthesis and study of model peptides, J. Biol. Chem. 258:4464–4471.PubMedGoogle Scholar
  45. Yang, C.-Y., Chan, S.-H., Gianturco, S. H., Bradley, W. A., Sparrow, J. T., Tanimura, M., Li, W.-H., Sparrow, D. A., DeLoof, H., Rosseneu, M., Lee, F.-S., Gu, Z.-W., Gotto, A. M., Jr., and Chan, L., 1986, Sequence, structure, receptor-binding domains and internal repeats of human apolipoprotein B-100, Nature 323:738–742.PubMedCrossRefGoogle Scholar
  46. Yokoyama, S., Fukushima, D., Kupferberg, J. P., Kezdy, F. J., and Kaiser, E. T., 1980, The mechanism of activation of lecithin:cholesterol acyltransferase by apolipoprotein A-I and an amphiphilic peptide, J. Biol. Chem. 255:7333–7337.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Emil T. Kaiser
    • 1
  1. 1.Late of the Laboratory of Bioorganic Chemistry and BiochemistryRockefeller UniversityNew YorkUSA

Personalised recommendations