Molecular Building Kit of Fused-Proline-Derived Peptide Mimetics Allowing Specific Adjustment of the Dihedral Psi Angle

Beitrag in einer Fachzeitschrift
(Originalarbeit)


Details zur Publikation

Autorinnen und Autoren: Einsiedel J, Lanig H, Waibel R, Gmeiner P
Zeitschrift: Journal of Organic Chemistry
Verlag: American Chemical Society
Jahr der Veröffentlichung: 2007
Band: 72
Seitenbereich: 9102-9113
ISSN: 0022-3263
Sprache: Englisch


Abstract


(Chemical Equation Presented) Proline-derived peptide mimetics have become an area of paramount importance in peptide and protein chemistry. Since protein crystal structures frequently display Ψ angles of 140-170° for prolyl moieties, our intention was to design a completely novel series of 2,3-fused-proline-derived lactams covering this particular conformational space. Extending our recently described toolset of spirocyclic reverse-turn mimetics, we synthesized pyrrolidinyl-fused seven-, eight-, and nine-membered unsaturated lactam model peptides taking advantage of Grubbs' ring-closing metathesis. Investigating the seven-membered lactam 3a by means of IR and NMR spectroscopy and semiempirical molecular dynamics simulations, we could not observe a U-turn conformation; however, increasing the ring size to give eight- and nine-membered congeners revealed moderate and high type II β-turn inducing properties. Interestingly, the conformational properties of our model systems depend on both the ring size of the fused dehydro-Freidinger lactam and the position of the endocyclic double bond. Superior reverse-turn inducing properties could be observed for the fused azacyclononenone 3e. According to diagnostic transanular NOEs, a discrete folding principle of the lactam ring strongly deviating from the regioisomeric lactams 3c,f explains the conformational behavior. Hence, we were able to establish a molecular building kit that allows adjustments of a wide range of naturally occurring proline Ψ angles and thus can be exploited to probe molecular recognition and functional properties of biological systems. © 2007 American Chemical Society.



FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Einsiedel, Jürgen Dr.
Lehrstuhl für Pharmazeutische Chemie
Gmeiner, Peter Prof. Dr.
Lehrstuhl für Pharmazeutische Chemie
Lanig, Harald PD Dr.
Exzellenz-Cluster Engineering of Advanced Materials
Waibel, Reiner Dr.
Lehrstuhl für Pharmazeutische Chemie


Zitierweisen

APA:
Einsiedel, J., Lanig, H., Waibel, R., & Gmeiner, P. (2007). Molecular Building Kit of Fused-Proline-Derived Peptide Mimetics Allowing Specific Adjustment of the Dihedral Psi Angle. Journal of Organic Chemistry, 72, 9102-9113. https://dx.doi.org/10.1021/jo701703e

MLA:
Einsiedel, Jürgen, et al. "Molecular Building Kit of Fused-Proline-Derived Peptide Mimetics Allowing Specific Adjustment of the Dihedral Psi Angle." Journal of Organic Chemistry 72 (2007): 9102-9113.

BibTeX: 

Zuletzt aktualisiert 2018-09-08 um 13:23