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UCB, a Belgian pharmaceutical/chemical company, founded an industrial site in 1996 in Bulle, Switzerland. Since the time of the creation of the enterprise, industrial activity has been expanded continuously and consists today of three production buildings with more than 70 employees in production and approx. 180 in total. In a preface to the description of the manufacturing activities some general remarks are made to highlight factors to be considered for a successful site selection. The conclusion is reached that the investment – as of today – has successfully met the expectations of the investor.

SynopsisWater-soluble, random copolymers containing L-glutamine and either N5-(3-hydroxypropy1)-L-glutamine or N5-(4-hydroxybutyl)-~-glutamine were synthesized, fractionated, and characterized. The thermally induced helix-coil transitions of these copolymers were studied in water. A short-range interaction theory was used to deduce the Zimm-Bragg parameters u and s for the helix-coil transition in poly(L-glutamine) in water from an analysis of the melting curves of the copolymers in the manner described in earlier papers. The computed values of s indicate that L-glutamine is helix-indifferent a t low temperature and a helix-destabilizing residue at high temperature in water. At all temperatures in the range of O-70°C, the glutamine residue promotes helix-coil boundaries since the computed value of u is large. INTRODUCTIONThe helical preferences for L-glutamine (L-Gln) are characterized here with a "host-guest" technique which has been applied to 16 other amino acids in this series of papers.1-20 The "host-gue~t~' technique utilizes a random copolymer which has a major constituent (or host residue) that is water-soluble and undergoes a thermally induced helix-to-coil transition between 0 and 70°C. The minor constituent (or guest residue) influences the helix-coil transition properties of the copolymer. From an analysis of the melting behavior of the copolymers, the Zimm-Bragg parameters21 c and s for the guest residues are calculated. In this study, both N 5 -(3-hydroxypropyl) -L-glutamine, Gln (PrOH), and N5-(4-hydroxybutyl) -Lglutamine, Gln(BuOH), were used as host residues and L-Gln was the guest residue.Although helix-coil stability constants have not been determined previously for L-Gln, copolymers of Gln and homopolymer derivatives of this+ Chemical Production, Pharmaceutical Division, Sandoz Ltd., Basel, Switzerland.* T o whom requests for reprints should be addressed. Biopolymers, Vol. 21,51-77 (1982) The syntheses of the water-soluble copolymers are described in the Experimental section, and the experimental characterization of these copolymers and their melting behavior in aqueous solution are presented in the Results section. The determination of the Zimm-Bragg parametersz1 for L-Gln in water from an analysis of the melting behavior is described in the Discussion section. The short-range interaction theory is found to provide an adequate description of the behavior of L-Gln when compared to that observed in previous conformational studies of L-Gln in proteins. EXPERIMENTAL Preparation and Characterization of the CopolymersCopolymers were prepared from poly(y-benzyl-L-glutamate) [Glu(OBzl)], by an amidation reaction in liquid ammonia or by copolymerization with N-carboxyanhydrides (NCAs) of N5-(4,4'-dimethoxydiphenylmethy1)-L-glutamine [ a b b r e~i a t e d~~ as Gln( Mbh)] and of y-benzyl-L-glutamate. For the former reaction, the remaining benzyl ester groups were exchanged with 3-aminopropanol in dioxane to give poly[N5-(3-hydroxypropyl)-~-glutamine-co-~-glutamine]. The 4,4'-dimethoxydiphenylmethyl ...

SynopsisThe host-guest technique has been applied to the determination of the helix-coil stability constants of two naturally occurring amino acids, L-alanine and L-leucine, in a nonaqueous solvent system. Random copolymers containing L-alanine and L-leucine, respectively, as guest residues and y-benzyl-L-glutamate as the host residue were synthesized. The polymers were fractionated and characterized for their amino acid content, molecular weight, and helix-coil transition behavior in a dichloroacetic acid (DCA)-1,2-dichloroethane (DCE) mixture. Two types of helix-coil transitions were carried out on the copolymers: solventinduced transitions in DCA-DCE mixtures at 25OC and thermally induced transitions in a 82:18 (wt %) DCA-DCE mixture. The thermally induced transitions were analyzed by statistical mechanical methods to determine the Zimm-Bragg parameters, g and s, of the guest residues. The experimental data indicate that, in the nonaqueous solvent, the L-alanine residue stabilizes the a-helical conformation more than the L-leucine residue does. This is in contrast to their behavior in aqueous solution, where the reverse is true. The implications of this finding for the analysis of helical structures in globular proteins are discussed.