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The aspartic acid bond changes to an p-aspartate bond frequently as a side-reaction during peptide synthesis and often as a post-translational modification of proteins. The formation of paspartate bonds is reported to play a major role not only in protein metabolism, activation and deactivation, but also in pathological processes such as deposition of the neuritic plaques of Alzheimer's disease. Recently, we reported how conformational changes following the aspartic-acidbond isomerization may help the selective aggregation and retention of the amyloid p peptide in affected brains (Fabian et al., 1994). In the current study we used circular dichroism, Fouriertransform infrared spectroscopy, and molecular modeling to characterize the general effect of the , & aspartate-bond formation on the conformation of five sets of synthetic model peptides. Each of the non-modified, parent peptides has one of the major secondary structures as the dominant spectroscopically determined conformation: a type I p turn, a type I1 p turn, short segments of a or 3,, helices, or extended p strands. We found that both types of turn structures are stabilized by the aspartic acid-bond isomerization. The isomerization at a terminal position did not affect the helix propensity, but placing it in mid-chain broke both the helix and the /?-pleated sheet with the formation of reverse turns. The alteration of the geometry of the lowest energy reverse turn was also supported by molecular dynamics calculations. The tendency of the aspartic acid-bond isomerization to stabilize turns is very similar to the effect of incorporating sugars into synthetic peptides and suggests a common feature of these post-translational modifications in defining the secondary structure of protein fragments.

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Die Synthese der Pentafluorphenylester von Boc-Aminosauren und geschiitzten Peptiden wird beschrieben. Das Ziel der Untersuchungen war die racemisierungsfreie Herstellung der Pentafluorphenylester von Modellpeptiden und deren Kupplungsreaktionen. The Utilization of Pentafluorophenyl Esters in Peptide SynthesesThe synthesis of pentafluorophenyl esters of Boc-amino acids and protected peptides is described. The aim of the investigations was to prepare racemate-free pentafluorophenyl esters of model peptides and to study their coupling reactions.Uber die hohe Reaktivitat von Pentafluorphenylestern wurde in mehreren Arbeiten berichtet 1-3). Die Vorteile dieser hohen Reaktivitat konnten vorzuglich beim Verknupfen groBerer Peptidbruchstucke ausgenutzt werden, so z. B. bei der Synthese von menschlichem ACTH mit korrigierter Sequenz und seiner Fragmente4). Bei dieser Synthese war jedoch die C-endstandige Aminosaure der acylierenden Peptide stets Glycin oder Prolin, es bestand also keine Gefahr der Racemisierung. Wir hielten es fur wichtig, diese Methode auf die Synthese anderer Peptide auszudehnen.Fur unsere Synthesen waren Pentafluorphenylester von Boc-Aminosauren uner-1aBlich. Diese wurden mit Hilfe von DCC hergestellt. Die Daten einiger Boc-Aminosaure-pentafluorphenylester sind in Tabelle 1 angefiihrt. *) Korrespondenz bitte an diesen Autor richten.

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