Dedicated to Professor Richard Neidlein on the occasion of his 70th birthday b-Hexa-, b-hepta-, and b-nonapeptides, 1 ± 6, which carry functionalized side chains (CO 2 R, CO À 2 , (CH 2 ) 4 NH 3 , CH 2 ÀCHCH 2 ) consisting of b 3 -amino-acid residues of alternating configuration, or which carry geminal substituents in the 2-or 3-positions of all residues, have been synthesized (Schemes 1 ± 3), and their CD spectra in MeOH are reported (Figs. 2 ± 6). Strong Cotton effects (V > 10 5 ) are indicative of the presence of chiral secondary structures. It is suggested by simple modelling (Fig. 1) that the new b-peptides should not be able to fold to the familiar 3 14 -helical structures. Still, three of them (3, 4, and 5) give rise to CD spectra matching those of b-peptides that are known to be present as (M)-or (P)-3 14 -helices in MeOH solution. While possible folding motifs (Figs. 3,b, and 7) of the new b-peptides have been identified in crystal structures, an interpretation of the CD spectra has to be postponed until NMR solution structures become available. A list of all b-peptides giving rise to CD spectra with a minimum near 215 nm is included (Table).

Polymalatase from Physarum polycephalum calalysed the hydrolysis of b-poly [l-malate] and of the synthetic compounds b-di(l-malate), b-tetra(l-malate), b-tetra(l-malate) b-propylester, and l-malate b-methylester. Cyclic b-tri(l-malate), cyclic b-tetra(l-malate), and d-malate b-methylester were not cleaved, but were competitive inhibitors. The O-terminal acetate of b-tetra(l-malate) was neither a substrate nor an inhibitor. l-Malate was liberated; the K m, K i and V max values were measured. The appearance of comparable amounts of b-tri(l-malate), and b-di(l-malate) during the cleavage of b-tetra(l-malate) indicated a distributive mechanism for small substrates. The accumulation of a series of oligomers, peaking with the 11-mer and 12-mer in the absence of higher intermediates, indicated that the depolymerization of b-poly(l-malate) was processive. The results indicate that b-poly(l-malate) is anchored at its OH-terminus by the highly specific binding of the penultimate malyl residue. The malyl moieties beyond 12 residues downstream from the OH-terminus extend into a diffuse second, electrostatic binding site. The catalytic site joins the first binding site, accounting for the cleavage of the polymer into malate residues. It is proposed that the enzyme does not dissociate from b-poly(l-malate) during hydrolysis, when both sites are filled with the polymer. When only the first binding site is filled, the reaction partitions at each oligomer between hydrolysis and dissociation.Keywords: polymalatase; polymalate; depolymerase; synthetic substrates; inhibitors.The plasmodium of Physarum polycephalum and of other myxomycetes produces b-poly(l-malate) (PMLA), an unbranched polyester of l-malic acid [1,2]. The highly charged polyanion binds the replicative DNA polymerases, histones, and other nuclear proteins forming higher-order protein complexes in the nuclei of only these types of cells [3,4±6]. Plasmodia are multinucleated cells typical for myxomycetes in the vegetative branch of their life cycle [7]. Because they develop into cells of extreme sizes and yet display a high degree of synchrony in the timing of cellular events, PMLA has been proposed to function as a storage and carrier matrix in the maintenance of an adequate supply of proteins for all nuclei. In high PMLA-producer strains, the polymer is secreted into the culture medium and depolymerized to l-malate. The hydrolase (polymalatase) has been identified and characterized [8]. The catalytic activity has its optimum at pH 3.5. The large quantity of polymalatase found in the extract of the plasmodium probably refers to the zymogen, which is spontaneously activated during cell lysis [9].Protein chemistry and inhibitor studies have suggested a catalytic mechanism that is unusual for esterases [8]. Structure±function correlation studies with PMLA-derivatives have indicated that the enzyme cleaves the ester bonds while moving in a downstream direction from the OH-terminus [10]. Because of their hydrolytic instability, the employed inhibitors and substrates were...

The polyanionic poly[β-(S)-malic acids] (β-PMA) occur in slime molds (myxomycetes), black yeasts and other fungi and are involved in DNA replication. In order to be able to study the cleavage mechanism of β-PMA hydrolases, we have synthesized cyclic and linear oligomers of malic acid (β-OMA) consisting of up to eight residues. To this end, fragments with three different protecting groups were prepared, with allyl ester groups on the C-terminus, TBDPS groups at the O-terminus, and benzyl ester groups at the side chains (Schemes 2, 3, 7). Selective deprotection and fragment coupling (COCl 2 /C 5 H 5 N/CH 2 Cl 2 /-75°C) gave dimers, tetramers, and

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