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Modulating Collagen Triple-Helix Stability with 4-Chloro, 4-Fluoro, and 4-Methylprolines

  • Matthew D. Shoulders
  • Ronald T. Raines
Part of the Advances in Experimental Medicine and Biology book series (volume 611)

Introduction

Collagen is a fibrous protein comprising a right-handed, triple-helical bundle of three parallel, left-handed polyproline II-type helices. Each strand consists of approximately 300 repeats of the trimer (Xaa-Yaa-Gly), where Xaa is often (2S)-proline (Pro) and Yaa is often (2S,4R)-4-hydroxyproline (Hyp) [1]. The most abundant protein in vertebrates, collagen is of fundamental importance to the three-dimensional architecture of such animals. Understanding the chemical determinants of the structure and stability of collagen is essential for both curing collagen-related diseases and creating collagen-based biomaterials.

We have previously demonstrated that pyrrolidine ring pucker and thus triple-helical stability can be manipulated by functionalizing the γ-position of the proline ring with moieties that control the ring pucker via either steric or stereoelectronic effects (Figure 1). The presence of Hyp in the Yaa position of natural collagen greatly increases the stability...

Keywords

Triple Helix Collagenous Peptide Synthetic Collagen Collagen Triple Helix Stereoelectronic Effect 
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.

Notes

Acknowledgments

This work was supported by grant AR44276 (NIH). M.D.S. was supported by a graduate fellowship from the Department of Homeland Security.

References

  1. 1.
    Jenkins, C. L., Raines, R. T. Nat. Prod. Rep. 19, 49–59 (2002).CrossRefGoogle Scholar
  2. 2.
    Sakakibara, S., et al. Biochim. et Biophys. Acta 303, 198–202 (1973).Google Scholar
  3. 3.
    DeRider, M. L., et al. J. Am. Chem. Soc. 123, 777–778 (2001).CrossRefGoogle Scholar
  4. 4.
    Holmgren, S. K., et al. Nature 392, 666–667 (1998).CrossRefGoogle Scholar
  5. 5.
    Shoulders, M. D., Hodges, J. A., Raines, R. T. J. Am. Chem. Soc. 128, 8112–8113 (2006).CrossRefGoogle Scholar
  6. 6.
    Hodges, J. A., Raines, R. T. J. Am. Chem. Soc. 125, 9262–9263 (2003).CrossRefGoogle Scholar
  7. 7.
    Berger, Y., et al. J. Med. Chem. 48, 483–498 (2005).CrossRefGoogle Scholar
  8. 8.
    Hodges, J. A., Raines, R. T. J. Am. Chem. Soc. 127, 15923–15932 (2005).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Matthew D. Shoulders
    • 1
  • Ronald T. Raines
    • 1
    • 2
  1. 1.Department of ChemistryUniversity of Wisconsin-MadisonMadisonUSA
  2. 2.Department of BiochemistryUniversity of Wisconsin-MadisonMadisonUSA

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