Taylor, John

Associate Professor

John Taylor

Phone: 848-445-0514

E-mail: E-mail

FAX: 732-445-5312

Office: Wright Rieman Labs 278/292

Mail: Chemistry & Chemical Biology, 610 Taylor Road, Piscataway, NJ 08854


  • B.A. 1978, Oxford
  • Ph.D. 1983, Chicago
  • Postdoctoral Fellow, Nice 1983-84
  • Postdoctoral Associate, Max-Planck-Institute fur Experimentelle Medizin 1984-85
  • Assistant Professor, Rockefeller University 1985-91

Research Summary

A major objective of the lab is the development of approaches to understanding the functional conformations of intermediate-sized, flexible peptides with important biological activities. Our basic approach to this problem is the design, synthesis and study of peptide analogues. New methods in solid-phase peptide synthesis are being developed in order to synthesize peptides that are constrained in particular conformations by multiple side-chain to side-chain bridges. For example, lactam bridges linking lysine and aspartic acid residues in i and i+4 positions in the peptide chain are being used to stabilize amphiphilic alpha-helical structures in the peptide hormones beta-endorphin and calcitonin, as well as DNA-binding helical structures such as the basic region from the transcription factor GCN4. More complex structures of this type, simultaneously linking three or four side-chains, are also under development. An important aspect of our strategy is the use of detailed analyses of peptide conformations, by circular dichroism and NMR methods, and of receptor affinities, in order to evaluate the structural and energetic effects of our conformational constraints. In an extension of these studies, we are also investigating helix-stabilized analogues of the transmembrane domains of peptide hormone receptors. The goal of this work is to characterize the helix-helix interactions that define the core of the folded structures of this important class of proteins. Initially, this area of research is focused on the human receptors for opioid peptides such as beta-endorphin, dynorphin and the enkephalins.

Conformationally constrained peptides

A new area in which our research on conformationally constrained peptides has focused is in the design of peptide-based vaccines directed against HIV-1. In this project, we are exploring structure-activity relationships in the binding of an HIV-neutralizing human monoclonal antibody, 2F5, to its recognition epitope on the HIV envelope glycoprotein gp 41. The goal of this project is to develop conformationally constrained analogs of this epitope peptide that bind tightly to 2F5. We are then conjugating these peptides to carrier proteins, so that they can be recognized by the immune system, and we are testing their abilities to elicit an immune response that is (like that of 2F5) HIV neutralizing. These are the initial steps that we hope will lead to potential therapeutic applications in the treatment of HIV-positive patients, and prevention of the development of AIDS.

Properties of peptides at interfaces

In addition to our synthetic approaches, we are also developing model systems for studying the properties of peptides at interfaces. This area of research is being applied in particular to peptide hormones and to peptide segments of serum apolipoproteins that are implicated in either phospholipid binding or in the deposition of low density lipoproteins (LDL) onto damaged arterial walls. The air-water interface of a Langmuir trough and the phospholipid surfaces of single-bilayer vesicles are being used as model interfaces to which such peptides may be bound and studied.

Synthesis and structure of designed polypeptides

Synthesis and structure of designed polypeptidesThe above illustration is of the alpha-helical conformation of a protected synthetic bicyclic peptide, Boc-cyclo(1-5, 2-6)-[Lys-Lys-Ala-Ala-Asp-Asp]-OPac, in a trifluoroethanol/water (1/1) solution. The backbone atoms are traced by a solid green ribbon. Also apparent are the two lactam bridges linking the Lys(1) and Asp(5) side-chains and the Lys(2) and Asp(6) side chains. The molecule is oriented with the N-terminal Boc protecting group at the top, and the C-terminal OPac protecting group at the bottom. These groups can be removed to allow linkage of this peptide to other synthetic peptides for initiation and stabilization of the alpha-helical conformation. The structure of this hexapeptide was determined by 2-D NMR methods in the laboratory of Professor Jean Baum, also in this department, and is described in the 1994 publication by Bracken et al. listed below.






  1. Kazantzis, A., Waldner, M, Taylor, J. W., and Kapurniotu, A.: Conformationally constrained human calcitonin (hCt) analogues reveal a critical role of sequence 17-21 for the oligomerization state and bioactivity of hCt. Submitted for publication
  2. Taylor, J. W., Jin, Q. K., Sbacchi, M., Wang, L., Belfiore, P., Garnier, M., Kazantzis, A., Kapurniotu, A., Zaratin, P. F. and Scheideler, M. A.: Side-chain lactam-bridge conformational constraints differentiate the actions of salmon and human calcitonins and reveal a new design concept for potent calcitonin analogs. Submitted for publication.
  3. Zhang, M., Wu, B., Zhao, H. and Taylor, J. W.: The effect of C-terminal helix stabilization on specific DNA binding by monomeric GCN4 peptides. Submitted for publication.
  4. Tian, Y., Ramesh, C.V., Ma, X., Patel, T., Tiscione, M., Cenizal, T., Taylor, J.W.; Arnold, G.F., and Arnold, E.: Affinity of the HIV-1-neutralizing monoclonal antibody 2F5 for gp41 ELDKWA peptide analogues. In: Peptides: The Wave of the Future; Proc. 2nd International / 17th American Peptide Symposium (G. Barany, G. B. Fields, R. A. Houghten & M. Lebl, eds.), manuscript accepted, June, 2001.
  5. Taylor, J.W., Reddy, P., Patel, P. Dineen, T., and Naqvi, S.: Novel synthesis and application of a protected bicyclic a-helix-initiating heptapeptide suitable for segment condensation syntheses: Utility of pentaaminecobalt(III) for carboxyl protection. In: Peptides: The Wave of the Future; Proc. 2nd International / 17th American Peptide Symposium (G. Barany, G. B. Fields, R. A. Houghten & M. Lebl, eds.), manuscript accepted, June, 2001
  6. M. Zhang, B. Wu, J. Baum, and J. Taylor. "Conformational Characterization of a Helix-Nucleated Bicyclic GCN4 Decapeptide by Proton NMR", Journal of Peptide Research, 55, 398-408, 2000.
  7. Xie, L., and Taylor, J. W. Synthetic peptides designed to probe the structure and folding of opioid receptors. Proc. 16th Amer. Peptide Symp. (G. B. Fields, J. P. Tam & G. Barany, eds.), Kluwer Academic Publishers, Boston, 2000, pp.372-373.
  8. Taylor, J. W., Greenfield, N. J., Wu, B., Yu, Y. B. and Privalov, P. A calorimetric study of the helix-coil transition using a side-chain bridged peptide that folds and unfolds cooperatively. Proc. 16th Amer. Peptide Symp. (G. B. Fields, J. P. Tam & G. Barany, eds.), Kluwer Academic Publishers, Boston, 2000, pp 280-282
  9. Zhang, M., Yu, C., Baum, J. and Taylor, J. W. 1H-NMR structure of a model 14-residue peptide incorporating a rigid, helix-stabilizing, (i, i+7)-side-chain bridge. Proc. 16th Amer. Peptide Symp. (G. B. Fields, J. P. Tam & G. Barany, eds.), Kluwer Academic Publishers, Boston, 2000, pp. 283-284.
  10. Yu, C. and Taylor, J. W.: Synthesis and study of peptides with semirigid i and i+7 side-chain bridges designed for a-helix stabilization. Bioorg. Med. Chem. 7, 161-175, 1999.
  11. Taylor, J. W., Greenfield, N. J., Wu, B. and Privalov, P. A calorimetric study of the unfolding of an alpha-helix with covalently closed N- and C-terminal loops. J. Mol. Biol. 291, 965-976, 1999.
  12. Kayed, R., Taylor, J. W., Voelter, W. and Kapurniotu, A.: Rational design, conformational studies and bioactivity of highly potent, conformationally constrained calcitonin analogues. Eur. J. Biochem. 265, 606-618, 1999.
  13. Zhang, W. and Taylor, J. W.: Efficient solid-phase synthesis of peptides with tripodal side-chain bridges and optimization of the solvent conditions for solid-phase cyclizations. Tetrahedron Lett. 37, 2173-2176, 1996
  14. Yu, C. and Taylor, J. W.: A new strategy applied to the synthesis of an a-helical bicyclic peptide constrained by two overlapping i, i+7 side-chain bridges of novel design. Tetrahedron Lett. 37, 1731-1734, 1996.
  15. Kapurniotu, A. and Taylor, J. W.: Structural and conformational requirements for human calcitonin activity: design, synthesis and study of lactam-bridged analogues. J. Med. Chem. 38, 836-847 1995.
  16. Bracken, C., Guly�s, J., Taylor, J. W. and Baum, J.: Synthesis and NMR structure determination of an alpha-helical, bicyclic, lactam-bridged hexapeptide. J. Amer. Chem. Soc., 116, 6431-6432, 1994.
  17. Flach, C. R., Brauner, J. W., Taylor, J. W., Baldwin, R. C. and Mendelsohn, R.: External reflection FT-IR of peptide monolayer films in situ at the air/water interface: Experimental design, spectra-structure correlations and effects of hydrogen-deuterium exchange. Biophys. J., 67, 402-410, 1994.
  18. Taylor, J. W., Shih, I.-L., Lees, A. M. and Lees, R. S.: Surface-induced conformational switching in amphiphilic peptide segments of Apolipoproteins B and E and model peptides. Int. J. Peptide Protein Res., 41, 536-547, 1993

Research Area(s): 
Biophysical Chemistry
Organic Chemistry