Skip to main content
SpringerLink
Log in

Peptide β-Bend and 3 10 -Helix: from 3D-Structural Studies to Applications as Templates

  • Review Article
  • Published:
Journal of inclusion phenomena and macrocyclic chemistry Aims and scope Submit manuscript

Abstract

The 3 10-helix is a relatively common secondary structure motif in peptides and proteins. Its building block is one of various types of β-bend conformation which comprises an N α-acylated dipeptide alkylamide system. A complete 3D-structural characterization of this ternary helix has been achieved, thus allowing its unambiguous discrimination from the closely related α-helix. Recent applications of rigidified peptide β-bends and 3 10-helices as templates for investigations in synthetic organic chemistry (macrocyclization, catalysis), host–guest chemistry (molecular recognition), and physical chemistry (donor–acceptor interaction) will be discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

Ac:

acetyl

Agl:

Cα-allylglycine

Aib:

α-aminoisobutyric acid (or Cα,α-dimethylglycine)

(αMe)Phg:

Cα-methyl, Cα-phenylglycine

(αMe)Val:

Cα-methyl valine

Api:

4-amino-4-carboxypiperidine

ATANP:

2-amino-3-[1-(1,4,7-triazacyclononane)] propanoic acid

Bin:

2′,1′:1,2;1′′,2′′:3,4-dinaphthcyclohepta-1,3-diene-6-amino-6-carboxylic acid

Boc:

tert-butyloxycarbonyl

Bpa:

para-benzoyl-phenylalanine

Bz:

benzoyl

DMSO:

dimethylsulfoxide

ESR:

electron spin resonance

Fmoc:

fluoren-9-ylmethyloxycarbonyl

hhMag:

homo-homo-Mag

hMag:

homo-Mag

Mag:

Cα-methyl, Cα-allylglycine

NHBzl:

benzylamino

NHMe:

methylamino

NHtBu:

tert-butylamino

OMe:

methoxy

OtBu:

tert-butoxy

pBrBz:

para-bromobenzoyl

Z:

benzyloxycarbonyl

RCM:

ring-closing metathesis

TEMPO:

2,2,6,6-tetramethylpiperidinyl-1-oxy

TOAC:

2,2,6,6-tetramethylpiperidine-1-oxy-4-amino-4-carboxylic acid

Tren:

tris-(2-aminoethyl)amine

References

  1. (a) C. Toniolo, F. Formaggio, M. Crisma, G. Valle, W.H.J. Boesten, H.E. Schoemaker, J. Kamphuis, P.A. Temussi, E.L. Becker, and G. Précigoux: Tetrahedron 49, (3641) ((1993)). (b) C. Toniolo, A. Bianco, F. Formaggio, M. Crisma, G.M. Bonora, E. Benedetti, V. Del Duca, M. Saviano, B. Di Blasio, C. Pedone, and A. Aubry: Bioorg. Med. Chem. 3, 1211 (1995). (c) M. Crisma, A. Bianco, F. Formaggio, C. Toniolo, and J. Kamphuis: Lett. Pept. Sci. 2, 187 (1995)

  2. (a) C.M. Venkatachalam: Biopolymers 6, 1425 (1968). (b) C. Toniolo: CRC Crit. Rev. Biochem. 9, 1 (1980). (c) G.D. Rose, L.M. Gierasch, and J.A. Smith: Adv. Protein Chem. 37, 1 (1985)

  3. (a) C. Toniolo and E. Benedetti: Trends Biochem. Sci. 16, 350 (1991). (b) D.J. Barlow and J.M. Thornton: J. Mol. Biol. 201, 601 (1988). (c) I.L. Karle and P. Balaram: Biochemistry 29, 6747 (1990). (d) M.E. Karpen, P.L. de Haseth, and K.E. Neet: Protein Sci. 1, 1333 (1992). (e) G.L. Millhauser: Biochemistry 34, 3873 (1995). (f) K.A. Bolin and G.L. Millhauser: Acc. Chem. Res. 32, 1027 (1999). (g) L. Pal and G. Basu: Protein Eng. 12, 811 (1999). (h) L. Pal, G. Basu, and P. Chakrabarti: Proteins: Struct. Funct. Genet. 48, 571 (2002). (i) L. Pal, P. Chakrabarti, and G. Basu: J. Mol. Biol. 326, 273 (2003)

  4. (a) E. Benedetti, A. Bavoso, B. Di Blasio, V. Pavone, C. Pedone, C. Toniolo, and G.M. Bonora: Proc. Natl. Acad. Sci. USA 79, 7951 (1982). (b) R. Nagaraj and P. Balaram: Acc. Chem. Res. 14, 356 (1981). (c) S. Rebuffat, C. Goulard, B. Bodo, and M.-F. Roquebert: Recent Res. Devel. Org. Biorg. Chem. 3, 65 (1999). (d) C. Toniolo, M. Crisma, F. Formaggio, C. Peggion, A.F. Epand, and R.M. Epand: Cell. Mol. Life Sci. 58, 1179 (2001). (e) C. Peggion, F. Formaggio, M. Crisma, R.F. Epand, R.M. Epand, and C. Toniolo: J. Pept. Sci.9, 679 (2003)

  5. H.S. Taylor (1941) Proc. Am. Phyl. Soc. 85 1 Occurrence Handle1:CAS:528:DyaH38XhtFKlug%3D%3D

    CAS  Google Scholar 

  6. L. Pauling R.B. Corey H.R. Branson (1951) Proc. Natl. Acad. Sci. USA 37 205 Occurrence Handle1:CAS:528:DyaG3MXktVCqtg%3D%3D Occurrence Handle14816373

    CAS  PubMed  Google Scholar 

  7. L. Bragg J.C. Kendrew M.F. Perutz (1950) Proc. R. Soc. London A 203 321

    Google Scholar 

  8. (a) V. Pavone, G. Gaeta, A. Lombardi, F. Nastri, O. Maglio, C. Isernia, and M. Saviano: Biopolymers 38, 705 (1996). (b) R.T. Wintjens, M.J. Rooman, and S.J. Wodak: J. Mol. Biol. 255, 235 (1996). (c) K.-L. Chou: Biopolymers 42, 837 (1997). (d) C. Ramakrishnan and D.V. Nataraj: J. Pept. Sci. 4, 239 (1998)

  9. (a) M.L. Huggins: Chem. Rev. 32, 195 (1943). (b) J. Donohue: Proc. Natl. Acad. Sci. USA 39, 470 (1953). (c) G.N. Ramachandran, C.M. Venkatachalam, and S. Krimm: Biophys. J. 66, 849 (1966). (d) E.N. Baker and R.E. Hubbard: Progr. Biophys. Mol. Biol. 44, 97 (1984)

  10. (a) M. Marino, L. Braun, P. Cossart, and P. Ghosh: Mol. Cell. 4, 1063 (1999). (b) M. Marino, L. Braun, P. Cossart, and P. Ghosh: Proc. Natl. Acad. Sci. USA 4, 8784 (2000). (c) J.W. Peters, M.H.B. Stowell, and D.C. Rees: Nature: Struct. Biol. 3, 991 (1996). (d) B. Kobe: Nature: Struct. Biol. 3, 977 (1996). (e) B. Kobe and A.V. Kajava: Trends Biochem. Sci. 25, 509 (2000). (f) B. Kobe and A.V. Kajava: Curr. Opin. Struct. Biol. 11, 725 (2001). (g) A.V. Kajava and B. Kobe: Protein Sci. 11, 1082 (2002)

  11. G.R. Marshall: In N. Kharasch (ed.), Intra-Science Chemistry Report (Vol. 5), Gordon and Breach (1971), pp. 305–316

  12. (a) N. Shamala, R. Nagaraj, and P. Balaram: J. Chem. Soc., Chem. Commun. 996 (1978). (b) C. Toniolo, M. Crisma, F. Formaggio, and C. Peggion: Biopolymers (Pept. Sci.) 60, 396 (2001)

  13. (a) V. Pavone, B. Di Blasio, A. Santini, E. Benedetti, C. Pedone, C. Toniolo, and M. Crisma: J. Mol. Biol. 214, 633 (1990). (b) C. Toniolo, M. Crisma, G.M. Bonora, E. Benedetti, B. Di Blasio, V. Pavone, C. Pedone, and A. Santini: Biopolymers 31, 129 (1991). (c) R. Gessmann, H. Brueckner, and K. Petratos: J. Pept. Sci. 9, 753 (2003)

  14. (a) M. Goodman, C. Toniolo, and P. Pallai: In B. Castro and J. Martinez (eds.), Forum Peptides, Dohr (1985), pp. 146-174. (b) V. Pavone, E. Benedetti, B. Di Blasio, C. Pedone, A. Santini, A. Bavoso, C. Toniolo, M. Crisma, and L. Sartore: J. Biomol. Struct. Dyn. 7, 1321 (1990). (c) G.R. Marshall, E.E. Hodgkin, D.A. Langs, G.D. Smith, J. Zabrocki, and M.T. Leplawy: Proc. Natl. Acad. Sci. USA 87, 487 (1990). (d) K. Okuyama, N. Tanaka, M. Doi, and M. Narita: Bull. Chem. Soc. Jpn. 61, 3115 (1988)

  15. C. Toniolo E. Benedetti (1991) Macromolecules 24 4004 Occurrence Handle10.1021/ma00014a006 Occurrence Handle1:CAS:528:DyaK3MXkt12rt7w%3D

    Article  CAS  Google Scholar 

  16. (a) C. Toniolo, G.M. Bonora, V. Barone, A. Bavoso, E. Benedetti, B. Di Blasio, P. Grimaldi, F. Lelj, V. Pavone, and C. Pedone: Macromolecules 18, 895 (1985). (b) D.F. Kennedy, M. Crisma, C. Toniolo, and D. Chapman: Biochemistry 30, 6541 (1991). (c) G. Yoder, A. Polese, R.A.G.D. Silva, F. Formaggio, M. Crisma, Q.B. Broxterman, J. Kamphuis, C. Toniolo, and T.A. Keiderling: J. Am. Chem. Soc. 119, 10278 (1997). (d) C. Toniolo, A. Polese, F. Formaggio, M. Crisma, and J. Kamphuis: J. Am. Chem. Soc. 118, 2744 (1996). (e) F. Formaggio, M. Crisma, P. Rossi, P. Scrimin, B. Kaptein, Q.B. Broxterman, J. Kamphuis and C. Toniolo: Chem. Eur. J. 6, 4498 (2000). (f) R. Gratias, R. Konat, H. Kessler, M. Crisma, G. Valle, A. Polese, F. Formaggio, C. Toniolo, Q.B. Broxterman, and J. Kamphuis: J. Am. Chem. Soc. 120, 4763 (1998). (g) S. Mammi, M. Rainaldi, M. Bellanda, E. Schievano, E. Peggion, Q.B. Broxterman, F. Formaggio, M. Crisma, and C. Toniolo: J. Am. Chem. Soc. 122, 11735 (2000)

    Google Scholar 

  17. (a) F. Donald, G. Hungerford, D.J.S. Birch, and B.D. Moore: Chem. Commun. 313 (1995). (b) G. Hungerford, M. Martinez-Insua, D.J.S. Birch, and B.D. Moore: Angew. Chem. Int. Ed. Engl. 37, 326 (1998). (c) P. Pengo, L. Pasquato, S. Moro, A. Brigo, F. Fogolari, Q.B. Broxterman, B. Kaptein, and P. Scrimin: Angew. Chem. Int. Ed. 42, 3388 (2003)

  18. (a) C.E. Schafmeister, J. Po, and G.L. Verdine: J. Am. Chem. Soc. 122, 5891 (2000). (b) H.E. Blackwell and J.H. Grubbs: Angew. Chem. Int. Ed. Engl. 37, 3281 (1998). (c) H.E. Blackwell, J.S. Sadowski, R.J. Howard, J.N. Sampson, J.A. Chao, W.E. Steinmetz, D.J. O’ Leary, and R.H. Grubbs: J. Org. Chem. 66, 5291 (2001). (d) S.J. Miller, H.E. Blackwell, and R.H. Grubbs: J. Am. Chem. Soc. 118, 9606 (1996). (e) B. Kaptein, Q.B. Broxterman, H.E. Schoemaker, F.P.J.T. Rutjes, J.J.N. Veerman, J. Kamphuis, C. Peggion, F. Formaggio, and C. Toniolo: Tetrahedron 57, 6567 (2001). (f) J. Pernerstorfer, M. Schuster, and S. Blechert: J. Chem. Soc., Chem. Commun. 1949 (1997). (g) A. Ravi, B.V. Venkataram Prasad, and P. Balaram: J. Am. Chem. Soc. 105, 105 (1983). (h) M. Saviano, E. Benedetti, R.M. Vitale, B. Kaptein, Q.B. Broxterman, M. Crisma, F. Formaggio, and C. Toniolo: Macromolecules 35, 4204 (2002)

  19. F. Formaggio M. Bonchio M. Crisma C. Peggion S. Mezzato A. Polese A. Barazza S. Antonello F. Maran Q.B. Broxterman B. Kaptein J. Kamphuis R.M. Vitale M. Saviano E. Benedetti C. Toniolo (2002) Chem. Eur. J. 8 84 Occurrence Handle10.1002/1521-3765(20020104)8:1<84::AID-CHEM84>3.0.CO;2-N Occurrence Handle1:CAS:528:DC%2BD38Xmt1ylsA%3D%3D

    Article  CAS  Google Scholar 

  20. (a) S.J. Miller, G.T. Copeland, N. Papaioannou, T.E. Horstmann, and E.M. Ruel: J. Am. Chem. Soc. 120, 1629 (1998). (b) G.T. Copeland, E.R. Jarvo, and S.J. Miller: J. Org. Chem. 63, 6784 (1998). (c) G.T. Copeland and S.J. Miller: J. Am. Chem. Soc. 121, 4306 (1999). (d) E.R. Jarvo, G.T. Copeland, N. Papaioannou, P.J. Bonitatebus, Jr., and S.J. Miller: J. Am. Chem. Soc. 121, 11638 (1999). (e) R.F. Harris, A.J. Nation, G.T. Copeland, and S.J. Miller: J. Am. Chem. Soc. 122, 11270 (2000). (f) J.T. Blank, D.J. Guerin, and S.J. Miller:Org. Lett. 2, 1247 (2000). (g) E.R. Jarvo, M.M. Vasbinder, and S.J. Miller: Tetrahedron 56, 9773 (2000). (h) M.M. Vasbinder, E.R. Jarvo, and S.J. Miller: Angew. Chem. Int. Ed. 40, 2824 (2001). (i) G.T. Copeland and S.J. Miller: J. Am. Chem. Soc. 123, 6496 (2001). (j) E.R. Jarvo, C.A. Evans, G.T. Copeland, and S.J. Miller: J. Org. Chem. 66, 5522 (2001)

  21. (a) P. Rossi, F. Felluga, P. Tecilla, F. Formaggio, M. Crisma, C. Toniolo, and P. Scrimin: J. Am. Chem. Soc. 121, 6948 (1999). (b) P. Rossi, F. Felluga, P. Tecilla, F. Formaggio, M. Crisma, C. Toniolo, and P. Scrimin: Biopolymers (Pept. Sci.) 55, 496 (2000). (c) C. Sissi, P. Rossi, F. Felluga, F. Formaggio, M. Palumbo, P. Tecilla, C. Toniolo, and P. Scrimin: J. Am. Chem. Soc. 123, 3169 (2001). (d) A. Scarso, U. Scheffer, M. Göbel, Q.B. Broxterman, B. Kaptein, F. Formaggio, C. Toniolo, and P. Scrimin: Proc. Natl. Acad. Sci. USA 99, 5144 (2002)

    Google Scholar 

  22. (a) M. Maggini, G. Scorrano, A. Bianco, and C. Toniolo: J. Chem. Soc., Chem. Commun. 305 (1994). (b) A. Bianco, F. Gasparrini, M. Maggini, D. Misiti, A. Polese, M. Prato, G. Scorrano, C. Toniolo, and C. Villani: J. Am. Chem. Soc. 119, 7550 (1997). (c) A. Bianco, C. Corvaja, M. Crisma, D.M. Guldi, M. Maggini, E. Sartori, and C. Toniolo: Chem. Eur. J. 8, 1544 (2002). (d) S.H. Friedman, D.L. De Camp, R.P. Sijbesma, G. Srdanov, F. Wudl, and G.L. Kenyon: J. Am. Chem. Soc. 115, 6506 (1993). (e) A. Bianco, T. Da Ros, M. Prato, and C. Toniolo: J. Pept. Sci. 7, 208 (2001)

    Google Scholar 

  23. (a) C. Toniolo, M. Crisma, and F. Formaggio: Biopolymers (Pept. Sci.) 47, 153 (1998). (b) C. Toniolo, E. Valente, F. Formaggio, M. Crisma, G. Pilloni, C. Corvaja, A. Toffoletti, G.V. Martinez, M.P. Hanson, G.L. Millhauser, C. George and J.L. Flippen-Anderson:J. Pept. Sci. 1, 45 (1995). (c) P. Hanson, G. Martinez, G. Millhauser, F. Formaggio, M. Crisma, C. Toniolo, and C. Vita: J. Am. Chem. Soc. 118, 271 (1996). (d) P. Hanson, G. Millhauser, F. Formaggio, M. Crisma, and C. Toniolo: J. Am. Chem. Soc. 118, 7618 (1996). (e) P. Hanson, D.J. Anderson, G. Martinez, G. Millhauser, F. Formaggio, M. Crisma, C. Toniolo, and C. Vita: Mol. Phys. 95, 957 (1998). (f) V. Monaco, F. Formaggio, M. Crisma, C. Toniolo, P. Hanson, G. Millhauser, C. George, J.R. Deschamps, and J.L. Flippen-Anderson: Bioorg. Med. Chem. 7, 119 (1999). (g) D.J. Anderson, P. Hanson, J. Mc Nulty, G. Millhauser, V. Monaco, F. Formaggio, M. Crisma, and C. Toniolo: J. Am. Chem. Soc. 121, 6919 (1999). (h) J.C. Mc Nulty, J.L. Silapie, M. Carnevali, C.T. Farrar, R.G. Griffin, F. Formaggio, M. Crisma, C. Toniolo, and G.L. Millhauser: Biopolymers(Pept. Sci.) 55, 479 (2000)

    Google Scholar 

  24. (a) C. Corvaja, E. Sartori, A. Toffoletti, F. Formaggio, M. Crisma, and C. Toniolo: Biopolymers (Pept. Sci.) 55, 486 (2000). (b) C. Corvaja, E. Sartori, A. Toffoletti, F. Formaggio, M. Crisma, C. Toniolo, J.-P. Mazaleyrat, and M. Wakselman: Chem. Eur. J. 6, 2775 (2000). (c) E. Sartori, A. Toffoletti, F. Rastrelli, C. Corvaja, A. Bettio, F. Formaggio, S. Oancea, and C. Toniolo: J. Phys. Chem. A107, 6905 (2003)

  25. (a) B. Pispisa, A. Palleschi, L. Stella, M. Venanzi, and C. Toniolo: J. Phys. Chem. B102, 7890 (1998). (b) C. Toniolo, F. Formaggio, M. Crisma, J.-P. Mazaleyrat, M. Wakselman, C. George, J.R. Deschamps, J.L. Flippen-Anderson, B. Pispisa, M. Venanzi, and A. Palleschi: Chem. Eur. J. 5, 2254 (1999). (c) B. Pispisa, L. Stella, M. Venanzi, A. Palleschi, F. Marchiori, A. Polese, and C. Toniolo: Biopolymers 53, 169 (2000). (d) B. Pispisa, C. Mazzuca, A. Palleschi, L. Stella, M. Venanzi, F. Formaggio, C. Toniolo, J.-P. Mazaleyrat, and M. Wakselman: J. Fluoresc. 13, 139 (2003). (e) B. Pispisa, C. Mazzuca, A. Palleschi, L. Stella, M. Venanzi, M. Wakselman, J.-P. Mazaleyrat, M. Rainaldi, F. Formaggio, and C. Toniolo: Chem. Eur. J. 9, 4084 (2003)

Download references

Author information

Authors and Affiliations

  1. Institute of Biomolecular Chemistry, CNR, Department of Chemistry, University of Padova, 35131, Padova, Italy

    Claudio Toniolo, Marco Crisma, Fernando Formaggio & Cristina Peggion

  2. DSM Pharma Chemicals, Advanced Synthesis and Catalysis, P.O. Box 18, 6160, MD, Geleen, The Netherlands

    Quirinus Broxterman & Bernard Kaptein

Authors
  1. Claudio Toniolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marco Crisma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fernando Formaggio
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cristina Peggion
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Quirinus Broxterman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bernard Kaptein
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Claudio Toniolo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Toniolo, C., Crisma, M., Formaggio, F. et al. Peptide β-Bend and 3 10 -Helix: from 3D-Structural Studies to Applications as Templates. J Incl Phenom Macrocycl Chem 51, 121–136 (2005). https://doi.org/10.1007/s10847-004-0912-z

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10847-004-0912-z

Keywords

Search

Navigation