Abstract
Peptide foldamers are synthetic oligopeptides which attain a few, specific, constrained conformations in solution. Here, we review our contributions to the study of the structural features of several foldamers, comprising Cα-tetrasubstituted aminoacids, by spectroscopic techniques and, in particular, by a combined approach employing time-resolved energy transfer (FRET) experiments and molecular modeling to determine interprobe distances and orientations. Our data show that, for rigid systems, the commonly used assumption of random orientation of donor and acceptor is unjustified, and that in these cases a correct evaluation of the orientation factor is mandatory for meaningful structural determinations. Finally, we illustrate some applications of peptide foldamers in studies on the kinetics of protein folding and on the realization of peptide-based molecular devices.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Gellman, S.H. (1998) Foldamers: a manifesto. Acc. Chem. Res. 31, 173–180.
Cheng, R.P. (2004) Beyond de novo protein design – de novo design of non-natural folded oligomers. Curr. Opin. Struct. Biol. 14, 512–520.
Crisma, M., Formaggio, F., Moretto, A. and Toniolo, C. (2006) Peptide helices based on α-amino acids. Biopolymers 84, 3–12.
Cubberley, M.S. and Iverson, B.L. (2001) Models of higher-order structure: foldamers and beyond. Curr. Opin. Chem. Biol. 5, 650–653.
Licini, G., Prins, L. and Scrimin, P. (2005) Oligopeptide foldamers: from structure to function. Eur. J. Org. Chem. 969–977.
Sanford, A.R., Yamato, K., Yang, X., Yuan, L., Han, Y. and Gong, B. (2004) Well-defined secondary structures. Information-storing molecular duplexes and helical foldamers based on unnatural peptide backbones. Eur. J. Biochem. 271, 1416–1425.
Toniolo, C., Crisma, M., Formaggio, F., Peggion, C., Broxtermann, Q.B. and Kaptein, B. (2004) Molecular spacers for physicochemical investigations based on novel helical and extended peptide structures. Biopolymers 76, 162–176.
Kleinkauf, H. and von Döhren, H. (1990) Nonribosomal biosynthesis of peptide antibiotics. Eur. J. Biochem. 192, 1–15.
Aravinda, S., Shamala, N., Roy, R.S. and Balaram, P. (2003) Non-protein amino acids in peptide design. Proc. Indian Acad. Sci. (Chem. Sci.) 115, 373–400.
Toniolo, C., Crisma, M., Formaggio, F. and Peggion, C. (2001) Control of peptide conformation by the Thorpe-Ingold effect (Cα-tetrasubstitution). Biopolymers 60, 396–419.
Marshall, G.R. (1971) Studies on the biologically active conformations of angiotensin. In N. Kharasch (Ed.), Intra-Science Chemistry Report. Gordon and Breach, New York, pp. 305–316.
Pispisa, B., Palleschi, A., Venanzi, M. and Zanotti. G. (1996) Conformational statistics and energetic analysis of sequential peptides undergoing intramolecular transfer of excitation energy. J. Phys. Chem. B 100, 6835–6844.
Pispisa, B., Palleschi, A., Stella, L., Venanzi, M. and Toniolo, C. (1998) A nitroxide derivative as a probe for conformational studies of short linear peptides in solution. A spectroscopic and molecular mechanics investigation. J. Phys. Chem. B 102, 7890–7898.
Toniolo, C., Formaggio, F., Crisma, M., Mazaleyrat, J.P., Wakselman, M., George, C., Deschamps, J.R., Flippen-Anderson, J.L., Pispisa, B., Venanzi, M. and Palleschi, A. (1999) First peptide-based system of rigid donor – rigid interchromophore spacer – rigid acceptor: a structural and photophysical study. Chem. Eur. J. 5, 2254–2264.
Pispisa, B., Mazzuca, C., Palleschi, A., Stella, L., Venanzi, M., Formaggio, F., Polese, A. and Toniolo, C. (2000) Structural features of linear, (αMe)Val-based peptides in solution by photophysical and theoretical conformational studies. Biopolymers 55, 425–435.
Pispisa, B., Palleschi, A., Stella, L., Venanzi, M., Formaggio, F., Polese, A. and Toniolo, C. (2000) Structural features of linear, homo-Aib based peptides in solution. A spectroscopic and molecular mechanics investigation. J. Pept. Res. 56, 298–306.
Pispisa, B., Stella, L., Venanzi, M., Palleschi, A., Viappiani, C., Polese, A., Formaggio, F. and Toniolo, C. (2000) Quenching mechanisms in bichromophoric, 310-helical Aib-based peptides, modulated by chain length-dependent topologies. Macromolecules 33, 906–915.
Pispisa, B., Stella, L., Venanzi, M., Palleschi, A., Marchiori, F., Polese, A. and Toniolo, C. (2000) A spectroscopic and molecular mechanics investigation on a series of Aib-based linear peptides and a peptide template, both containing tryptophan and a nitroxide derivative as probes. Biopolymers, 53, 169–181.
Stella, L. (2001) Comparisons between time-resolved fluorescence experiments and computer simulations. In G. M. Giacometti and G. Giacometti (Eds.) Spectroscopic Techniques in Biophysics. IOS Press, Amsterdam, 2001, pp. 89–103.
Pispisa, B., Palleschi, A., Mazzuca, C., Stella, L., Valeri, A., Venanzi, M., Formaggio, F., Toniolo, C. and Broxterman, Q.B. (2002) The versatility of combining FRET measurements and molecular mechanics results for determining the structural features of ordered peptides in solution. J. Fluoresc. 12, 213–217.
Pispisa, B., Mazzuca, C., Palleschi, A., Stella, L., Venanzi, M., Formaggio, F., Toniolo, C. and Broxterman, Q.B. (2002) Structural features and conformational equilibria of 310-helical peptides in solution by spectroscopic and molecular mechanics studies. Biopolymers 67, 247–250.
Pispisa, B., Palleschi, A., Stella, L., Venanzi, M., Formaggio, F., Toniolo, C. and Broxterman, Q.B (2002) Effects of helical distortions on the optical properties of amide NH infrared absorption in short peptides in solution. J. Phys. Chem. B 106, 5733–5738.
Pispisa, B., Mazzuca, C., Palleschi, A., Stella, L., Venanzi, M., Formaggio, F., Toniolo, C., Mazaleyrat, J.P. and Wakselman, M. (2003) Spectroscopic properties and conformational features of short linear peptides in solution. A fluorescence and molecular mechanics investigation. J. Fluoresc. 13, 139–147.
Pispisa, B., Mazzuca, C., Palleschi, A., Stella, L., Venanzi, M., Wakselman, M., Mazaleyrat, J.P., Rainaldi, M., Formaggio, F. and Toniolo, C. (2003) A combined spectroscopic and theoretical study of a series of conformationally restricted hexapeptides carrying a rigid binaphthyl-nitroxide donor-acceptor pair. Chem. Eur. J. 9, 2–11.
Venanzi, M., Valeri, A., Palleschi, A., Stella, L., Moroder, L., Formaggio, F., Toniolo, C. and Pispisa, B. (2004) Structural properties and photophysical behavior of conformationally constrained hexapeptides functionalized with a new fluorescent analog of tryptophan and a nitroxide radical quencher. Biopolymers 75, 128–139.
Toniolo, C. and Benedetti, E. (1991) The polypeptide 310-helix. Trends Biochem. Sci. 16, 350–353.
Toniolo, C., Formaggio, F., Tognon, S., Broxterman, Q.B., Kaptein, B., Huang, R., Setnicka, V., Keiderling, T.A., McColl, I.H., Hecht, L. and Barron, L.D. (2004) The complete chirospectroscopic signature of the peptide 310-helix in aqueous solution. Biopolymers 75, 32–45.
Andrews, D.L. and Demidov A.A. (1999) Resonance Energy Transfer. Wiley, Chichester.
Lakowicz, J.R. (1999) Principles of Fluorescence Spectroscopy. Kluwer, New York.
Lewis, F.D., Zhang, L. and Zuo, X. (2005) Orientation control of fluorescence resonance energy transfer using DNA as a helical scaffold. J. Am. Chem. Soc. 127, 10002–10003.
Yang, J. and Winnik, M.A. (2005) The orientation parameter for energy transfer in restricted geometries including block copolymer interfaces: a Monte Carlo study. J. Phys. Chem. B 109, 18408–18417.
Zeng, W., Seward, H.E., Málnási-Csizmadia, A., Wakelin, S., Woolley, R.J., Cheema, G.S., Basran, J., Patel, T.R., Rowe, A.J. and Bagshaw, C.R. (2006) Resonance energy transfer between green fluorescent protein variants: complexities revealed with myosin fusion proteins. Biochemistry 45, 10482–10491.
Crisma, M., Deschamps, J.R., George, C., Flippen-Anderson, J.L., Kaptein, B., Boxterman, Q.B., Moretto, A., Oancea, S., Jost, M., Formaggio, F. and Toniolo, C. (2005) A topographic and conformationally constrained, spin-labeled, α-amino acid: a crystallographic characterization in peptides. J. Pept. Res. 65, 564–579.
Kubelka, J., Hofrichter, J. and Eaton, W.A. (2004) The protein folding “speed limit”. Curr. Opin. Struct. Biol. 14, 76–88.
Snow, C.D., Nguyen, H., Pande, V.S. and Gruebele, M. (2002) Absolute comparison of simulated and experimental protein-folding dynamics. Nature 420, 102–106.
Eaton, W.A., Muñoz, V., Hagen, S.J., Jas, G.S., Lapidus, L.J., Henry E.R. and Hofrichter, J. (2000) Fast kinetics and mechanisms in protein folding. Annu. Rev. Biophys. Biomol. Struct. 29, 327–359.
Stella, L., Mazzuca, C., Venanzi, M., Palleschi, A., Didonè, M., Formaggio, F., Toniolo, C. and Pispisa, B. (2004). Aggregation and water-membrane partition as major determinants of the activity of the antibiotic peptide trichogin GA IV. Biophys. J. 86, 936–945.
Mazzuca, C., Stella, L., Venanzi, M., Formaggio, F., Toniolo, C. and Pispisa, B. (2005) Mechanism of membrane activity of the antibiotic trichogin GA IV: a two-state transition controlled by peptide concentration. Biophys. J. 88, 3411–3421.
Gatto, E., Mazzuca, C., Stella, L., Venanzi, M., Toniolo, C. and Pispisa, B. (2006) Effect of peptide lipidation on membrane perturbing activity: a comparative study on two trichogin analogues. J. Phys. Chem. B. 110, 22813–22818.
Toniolo, C., Peggion, C., Crisma, M., Formaggio, F., Shui, X. and Eggleston, D.S. (1994) Structure determination of racemic trichogin A IV using centrosymmetric crystals. Nat. Struct. Biol. 1, 908–914.
Auvin-Guette, C., Rebuffat, S., Prigent, Y. and Bodo, B. (1992) Trichogin A IV, an 11-residue lipopeptaibol from Trichoderma longibrachiatum. J. Am. Chem. Soc. 114, 2170–2174.
Monaco, V., Locardi, E., Formaggio, F., Crisma, M., Mammi, S., Peggion, E., Toniolo, C., Rebuffat, S. and Bodo, B. (1998). Solution conformational analysis of amphiphilic helical, synthetic analogs of the lipopeptaibol trichogin GA IV. J. Pept. Res. 52, 261–272.
Venanzi, M., Gatto, E., Bocchinfuso, G., Palleschi, A., Stella, L., Formaggio, F. and Toniolo, C. (2006) Dynamics of formation of a helix-turn-helix structure in a membrane-active peptide: a time-resolved spectroscopic study. ChemBioChem 7, 43–45.
Venanzi, M., Gatto, E., Bocchinfuso, G., Palleschi, A., Stella, L., Baldini, C., Formaggio, F. and Toniolo, C. (2006) Peptide folding dynamics: a time-resolved study from the nanosecond to the microsecond time regime. J. Phys. Chem. B 110, 22834–22841.
Pace, G., Venanzi, M., Castrucci, P., Scarselli, M., De Crescenzi, M., Palleschi, A., Stella, L., Formaggio, F., Toniolo, C. and Marletta, G. (2006) Static and dynamic features of a helical hexapeptide chemisorbed on a gold surface. Mater. Sci. Eng. C. 27, 1309–1312.
Venanzi, M., Pace, G., Palleschi, A., Stella, L., Castrucci, P., Scarselli, M., De Crescenzi, M., Formaggio, F., Toniolo, C. and Marletta, G. (2006) Densely-packed self-assembled monolayers on gold surfaces from a conformationally constrained helical hexapeptide. Surf. Sci. 600, 409–416.
Gatto, E., Venanzi, M., Palleschi, A., Stella, L., Pispisa, B., Lorenzelli, L., Toniolo, C., Formaggio, F. and Marletta, G. (2006) Self-assembled peptide monolayers on interdigitated gold microelectrodes. Mater. Sci. Eng. C 27, 1309–1312.
Love, J.C., Estroff, L.A., Kriebel, J.K., Nuzzo, R.G. and Whitesides, G.M. (2005) Self-assembled monolayers of thiolates on metals as a form of nanotechnology. Chem. Rev. 105, 1103–1170.
Sia, S.K., Carr, P.A., Cochran, A.G., Malashkevich, V.N. and Kim, P.S. (2002) Short constrained peptides that inhibit HIV-1 entry. Proc. Natl. Acad. Sci. USA 99, 14664–14669.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Stella, L. et al. (2010). Peptide Foldamers: From Spectroscopic Studies to Applications. In: Geddes, C.D. (eds) Reviews in Fluorescence 2008. Reviews in Fluorescence 2008, vol 2008. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1260-2_17
Download citation
DOI: https://doi.org/10.1007/978-1-4419-1260-2_17
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4419-0828-5
Online ISBN: 978-1-4419-1260-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)