Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Facile synthesis of block copolypeptides of defined architecture

Abstract

Many natural polymeric materials (particularly structural proteins) display a hierarchy of structure over several length scales. Block copolymers are able to self-assemble into ordered nanostructures1,2, but the random-coiled nature of their polymer chains usually suppresses any further levels of organization. The use of components with regular structures, such as rigid-rod polymers, can increase the extent of spatial organization in self-assembling materials3. But the synthesis of such polymeric components typically involves complicated reaction steps that are not suitable for large-scale production. Proteins form hierarchically organized structures in which the fundamental motifs are generally α-helical coils and β-sheets4. Attempts to synthesize polypeptides with well-defined amino-acid sequences, which might adopt similar organized structures, have been plagued by unwanted side reactions5 that give rise to products with a wide range of molecular weights6,7,8,9,10, hampering the formation of well-defined peptide block copolymers11,12,13,14,15,16,17. Here I describe a polymerization strategy that overcomes these difficulties by using organonickel initiators which suppress chain-transfer and termination side reactions. This approach allows the facile synthesis of block copolypeptides with well-defined sequences, which might provide new peptide-based biomaterials with potential applications in tissue engineering, drug delivery and biomimetic composite formation.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Comparison of the abilities of different initiators to control molecular weight of PBLG as a function of initiator concentration in polymerizations of Glu-NCA: A, phenethylamine initiator; B, bipyNi(COD) initiator; C, sodium tert -butoxide initiator; D, theoretical molecular weight calculated from [M]0/[I]0.
Figure 2: Chromatogram of a PBLG0.78- b -PZLL0.22 diblock copolymer prepared by sequential addition of Lys-NCA and Glu-NCA to bipyNi(COD) initiator in DMF.

References

  1. 1

    Hillmyer, M. A. et al . Complex phase behavior in solvent-free nonionic surfactants. Science 271, 976–978 (1996).

    ADS  CAS  Article  Google Scholar 

  2. 2

    Matsen, M. W. & Bates, F. S. Origins of complex self-assembly in block copolymers. Macromolecules 29, 7641–7644 (1996).

    ADS  CAS  Article  Google Scholar 

  3. 3

    Stupp, S. I. et al . Supramolecular materials: self-organized nanostructurs. Science 276, 384–389 (1997).

    CAS  Article  Google Scholar 

  4. 4

    Fasman, G. D. Prediction of Protein Structure and the Principles of Protein Conformation(Plenum, New York, (1989)).

    Book  Google Scholar 

  5. 5

    Bamford, C. H., Elliot, A. & Hanby, W. E. Synthetic Polypeptides(Academic, New York, (1956)).

    Google Scholar 

  6. 6

    Cardinaux, F., Howard, J. C., Taylor, G. T. & Scheraga, H. A. Block copolymers of amino acids. I. Synthesis and structure of copolymers of l-alanine or l-phenylalanine with d,l-lysine- d 7or d,l-lysine. Biopolymers 16, 2005–2028 (1977).

    CAS  Article  Google Scholar 

  7. 7

    Howard, J. C., Cardinaux, F. & Scheraga, H. A. Block copolymers of amino acids. II. Physicochemical data on copolymers containing l-alanine or l-phenylalanine. Biopolymers 16, 2029–2051 (1977).

    CAS  Article  Google Scholar 

  8. 8

    Gratzer, W. B. & Doty, P. Aconformational examination of poly-l-alanine and poly-d,l-alanine in aqueous solution. J. Am. Chem. Soc. 85, 1193–1197 (1963).

    CAS  Article  Google Scholar 

  9. 9

    Inoue, K. et al . Preparation and conformation of hexaarmed star poly(β-benzyl-l-aspartates) utilizing hexakis(4-aminophenoxy) cyclotriphosphazene. J. Am. Chem. Soc. 116, 10783–10784 (1994).

    CAS  Article  Google Scholar 

  10. 10

    Kubota, S. & Fasman, G. D. The β conformation of polypeptides of valine, isoleucine, and threonine in solution and solid-state: optical and infrared studies. Biopolymers 14, 605–631 (1975).

    CAS  Article  Google Scholar 

  11. 11

    Kricheldorf, H. R. α-Aminoacid-N-Carboxyanhydrides and Related Materials(Springer, New York, (1987)).

    Book  Google Scholar 

  12. 12

    Kricheldorf, H. R. in Models of Biopolymers by Ring-Opening Polymerization(ed. Penczek, S.) (CRC, Boca Raton, (1990)).

    Google Scholar 

  13. 13

    Idelson, M. & Blout, E. R. Polypeptides XV. Infrared spectroscopy and the kinetics of the synthesis of polypeptides: primary amine initiated reactions. J. Am. Chem. Soc. 79, 3948–3957 (1957).

    CAS  Article  Google Scholar 

  14. 14

    Idelson, M. & Blout, E. R. Polypeptides XVIII. A kinetic study of the polymerization of amino acid N -carboxyanhydrides initiated by strong bases. J. Am. Chem. Soc. 80, 2387–2393 (1958).

    CAS  Article  Google Scholar 

  15. 15

    Lundberg, R. D. & Doty, P. Polypeptides XVII. A study of the kinetics of the primary amine-initiated polymerization of N -carboxyanydrides with special reference to configurational and stereochemical effects. J. Am. Chem. Soc. 79, 3961–3972 (1957).

    CAS  Article  Google Scholar 

  16. 16

    Deming, T. J. Polypeptide materials: new synthetic methods and applications. Adv. Mater. 9, 299–311 (1997).

    CAS  Article  Google Scholar 

  17. 17

    Deming, T. J. Transition metal–amine initators for preparation of well-defined poly(γ-benzyl-l-glutamate). J. Am. Chem. Soc. 119, 2759–2760 (1997).

    CAS  Article  Google Scholar 

  18. 18

    Fetters, L. J. in Encyclopedia of Polymer Science and Engineering 2nd edn 19–25 (Wiley-Interscience, New York, (1987)).

    Google Scholar 

  19. 19

    Webster, O. Living polymerization methods. Science 251, 887–893 (1991).

    ADS  CAS  Article  Google Scholar 

  20. 20

    Collman, J. P., Hegedus, L. S., Norton, J. R. & Finke, R. G. Principles and Applications of Organotransition Metal Chemistry 2nd edn(University Science, Mill Valley, (1987)).

    Google Scholar 

  21. 21

    Uhlig, E., Fehske, G. & Nestler, B. Z. Reaktionen cyclischer Carbonsaueureanhydride mit (α,α′-Dipyridyl)-(cyclooctadien-1,5)-nickel. Anorg. Allg. Chem. 465, 141–146 (1980).

    CAS  Article  Google Scholar 

  22. 22

    Sano, K., Yamamoto, T. & Yamamoto, A. Preparation of Ni- or Pt-containing cyclic esters by oxidative addition of cyclic carboxylic anhydrides and their properties. Bull. Chem. Soc. Jpn 57, 2741–2747 (1984).

    CAS  Article  Google Scholar 

  23. 23

    Castaño, A. M. & Echavarren, A. M. Reactivity of a nickelacycle derived from aspartic acid: alkylations, insertions, and oxidations. Organometalics 13, 2262–2268 (1994).

    Article  Google Scholar 

  24. 24

    Block, H. Poly(γ-benzyl-l-glutamate) and Other Glutamic Acid Containing Polymers(Gordon and Breach, New York, (1983)).

    Google Scholar 

  25. 25

    Noshay, A. & McGrath, J. E. Block Copolymers(Academic, New York, (1977)).

    Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Timothy J. Deming.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Deming, T. Facile synthesis of block copolypeptides of defined architecture. Nature 390, 386–389 (1997). https://doi.org/10.1038/37084

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing