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Summary and Conclusions

The starting point of this chapter was the need for synthetic methods that enable integration of biological and, in particular, protein design concepts into organic and macromolecular chemistry as a means to enhance control of the structure and properties of organic and polymeric materials. Three chemical strategies for the preparation of (poly)peptides have been discussed. The objective was to show that the utility of these methods goes beyond the preparation of biologically and phar-maceutically relevant substances and that they are attractive tools for the development of novel biologically-inspired supramolecular architectures and polymeric materials.

The most straightforward method discussed for peptide synthesis was the NCA

ring-opening polymerization. Because of its simplicity, this method has been extensively used for the preparation of hybrid block copolymers and other macro-molecular architectures. However, because NCA polymerization is hampered by chain-breaking, -transfer and -termination reactions, it neither affords perfectly monodisperse materials nor enables preparation of peptides with predictable molecular weights. Also, NCA polymerization does not enable control of the a-amino acid sequence of the resulting polypeptides. The synthetic ease of NCA polymerization is, therefore, at the expense of structural perfection and this method is only of restricted use for the preparation of truly biomimetic supramolecular structures or polymeric materials.

SPPS is a second method that has found application outside the traditional area of peptide synthesis and which has been used successfully for the preparation of

552 | 6.6 Chemical Approaches for the Preparation of Biologically-inspired Supramolecular Architectures CGGGEYRLQIRGRERFEMFRELNEALELKDAQAGKEPGG

folding

Fig. 6.6.5. Synthesis of a protein[2]catenane using native chemical ligation. (Adapted from Ref. [34]).

a variety of building blocks for biologically-inspired supramolecular architectures. In contrast with the NCA polymerization SPPS enables preparation of perfectly monodisperse peptides with precise control of a-amino acid sequence. For practical reasons, however, the utility of SPPS is restricted to peptides containing 50-60 a-amino acid residues. Because most proteins contain more than 60 a-amino acids, it is obvious that this limits the use of SPPS, e.g. for the total chemical synthesis of proteins.

A method that can bridge the gap between SPPS and NCA polymerization, i.e. which enables the preparation of high-molecular-weight and perfectly monodisperse peptides with well-defined a-amino acid sequences, is peptide ligation. Peptide ligation involves chemoselective coupling of unprotected peptide segments in aqueous media. Peptide ligation techniques have been used with great success in protein total synthesis and protein engineering. The advantage of peptide ligation in comparison with biological protein synthesis (which has not been considered in this chapter) is that it tolerates any unnatural a-amino acid and can also enable facile conjugation of peptides/proteins to synthetic non-biological oligomers/polymers. The potential of peptide ligation has so far been largely unnoticed outside the biochemical/chemical biology community. The possibility of preparing high-molecular-weight and perfectly monodisperse peptides with precisely defined a-amino acid sequences might, however, also enable access to unprecedented biologically-inspired supramolecular architectures and polymeric materials.

1 (a) H. Morawetz, Polymers - The Origins and Growth of a Science, John Wiley and Sons, New York, 1985; (b) Y. Furukawa, Inventing Polymer Science: Staudinger, Carothers and the Emergence of Macromolecular Chemistry, University of Pennsylvania Press, 1998.

2 J. A. Brydson, Plastic Materials, 5th edn., Butterworths, London, 1989.

3 (a) B. Alberts, D. Bray, J. Lewis, M. Raff, K. Roberts, J. D. Watson, Molecular Biology of the Cell, 3rd edn., Garland Publishing, New York, 1994; (b) C. Branden, J. Tooze, Introduction to Protein Structure, 2nd edn., Garland Publishing, New York, 1999.

4 For recent reviews see, e.g., (a) J. C. M. van Hest, D. A. Tirrell, Chem. Commun. 2001, 1897-1904; (b) H.-A. Klok, Angew. Chem. Int. Ed. 2002, 41, 1509-1513.

5 (a) H. Leuchs, Ber. Dtsch. Chem. Ges. 1906, 39, 857-861; (b) H. Leuchs, W. Manasse, Ber. Dtsch. Chem. Ges. 1907,

40, 3235-3249; (c) H. Leuchs, W. Geiger, Ber. Dtsch. Chem. Ges. 1908,

41, 1721-1726.

6 W. D. Fuller, M. S. Veriander, M. Goodman, Biopolymers 1976, 15, 1869-1871.

7 R. Katakai, Y. Iizuka, J. Org. Chem. 1985, 50, 715-716.

8 W. H. Daly, D. S. Poche, Tetrahedron Lett. 1988, 29, 5859-5862.

9 For comprehensive reviews see, e.g., (a) H. R. Kricheldorf, a-Aminoacid N-Carboxyanhydrides and related Heterocycles, Springer, Berlin, 1987; (b) T. J. Deming, J. Polym. Sci. Part A: Polym. Chem. 2000, 38, 3011-3018.

10 (a) B. Gallot, Prog. Polym. Sci. 1996, 21, 1035-1088; (b) H.-A. Klok, S. Lecommandoux, Adv. Mater. 2001, 13, 1217-1229.

11 (a) H. Kukuia, H. Schiaad, M. Antonietti, S. Förster, J. Am. Chem. Soc. 2002, 124, 1658-1663; (b) F. ChEcot, S. Lecommandoux, Y. Gnanou, H.-A. Klok, Angew. Chem. Int. Ed. 2002, 41, 1339-1343.

12 For a recent review see S. Fórster, T. Piantenberg, Angew. Chem. Int. Ed. 2002, 41, 688-714.

13 Y. P. Myer, Macromolecules 1969, 2, 624-628.

14 (a) T. J. Deming, Nature 1997, 390, 386-389; (b) T. J. Deming, Macromolecules 1999, 32, 4500-4502.

15 See, for example, (a) M. E. Yu, T. J. Deming, Macromolecules 1998, 31, 4739-4745; (b) K. R. Brzezinska, T. J. Deming, Macromolecules 2001, 34, 4348-4354; (c) K. R. Brzezinska,

S. A. Curtin, T. J. Deming, Macromolecules 2002, 35, 2970-2976.

16 A. P. Nówak, V. Breedveid, L. Pakstis, B. Ozbas, D. J. Pine, D. Póchan, T. J. Deming, Nature 2002, 417, 424-428.

17 D. J. Póchan, L. Pakstis, B. Ozbas, A. P. Nówak, T. J. Deming, Macro-molecules 2002, 35, 5358-5360.

18 J. N. Israeiachviii, Intermolecular and Surface Forces, 2nd edn. Academic Press, New York, 1991.

19 See, for example, (a) P. Berndt, G. B. Fieids, M. Tirreii, J. Am. Chem. Soc. 1995, 117, 9515-9522; (b) Y.-C. Yu, P. Berndt, M. Tirreii, G. B. Fieids, J. Am. Chem. Soc. 1996, 118, 1251512520; (c) Y.-C. Yu, M. Tirreii, G. B. Fieids, J. Am. Chem. Soc. 1998, 120, 9979-9987; (d) K. C. Lee, P. A. Carisón, A. S. Góidstein, P. Yager, M. H. Geib, Langmuir 1999, 15, 55005508; (e) J. S. Martinez, G. P. Zhang, P. D. Hóit, H.-T. Jung, C. J. Carranó, M. G. Haygóód, A. Butier, Science 2000, 287, 1245-1247; (f) T. Gore, Y. Dóri, Y. Taimón, M. Tirreii, H. Bianco-Peied, Langmuir 2001, 17, 5352-5360.

20 (a) J. D. Hartgerink, E. Beniash, S. I. Stupp, Science 2001, 294, 16841688; (b) J. D. Hartgerink, E. Beniash, S. I. Stupp, Proc. Natl. Acad. Sci. USA 2002, 99, 5133-5138.

21 See, for example, (a) M. J. Lawrence, Chem. Soc. Rev. 1994, 23, 417-424; (b) L. E. Bromberg, E. S. Ron, Adv. Drug Deliver. Rev. 1998, 31, 197-221; (c) A.

V. Kabanüv, V. Y. ÄiAKHüv, Crit. Rev. Ther. Drug Carr. Syst. 2002, 19, 1-72.

22 (a) G. W. M. Vandermeuien, H.-A. Kiok, Polym. Prepr. (Am. Chem. Soc. Div. Polym. Chem.) 2001, 42(2), 8485; (b) M. Pechar, P. KopeckovA, L. Joss, J. Kopecek, Macromol. Biosci. 2002, 2, 199-206; (c) H.-A. Kiok,

G. W. M. Vandermeuien, A. Rosier, Polym. Prepr. (Am. Chem. Soc. Div. Polym. Chem.) 2002, 43(2), 715-716.

23 For reviews see, e.g., (a) A. Lupas, Trends Biochem. Sci. 1996, 21, 375382; (b) W. D. Kohn, R. S. Hodges, Trends Biotechnol. 1998, 16, 379-389; (c) P. Burkhard, J. Stetefeid, S. V. Streikov, Trends Cell Biol. 2001, 11, 82-88.

24 J. Y. SU, R. S. HODGES, C. M. KAY, Biochemistry 1994, 33, 15501-15510.

25 See, e.g., (a) E. T. Kaiser, Acc. Chem. Res. 1989, 22, 47-54; (b) S. Aimoto, Curr. Org. Chem. 2001, 5, 45-87.

26 See, e.g., (a) P. E. Dawson, S. B. H. Kent, Annu. Rev. Biochem. 2000, 69, 923-960; (b) J. A. Borgia, G. B. Fieids, Trends Biotechnol. 2000, 18, 243-251; (c) J. P. Tam, J. Xu, K. D. Eom, Biopolymers (Pept. Sci.) 2001, 60, 194-205.

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