MMI 15 mg/d is suitable for mild and moderate GD, whereas MMI 30 mg/d is advisable for severe cases. PTU is not recommended for initial use.

Synopsiscu-Helical poly(L-glutamic acid) in a gel state was found to he easily converted to the antiparallel 0 form by heating. Two 0 forms were obtained, depending on the temperature of heating. Temperatures between 40' and 85°C produced a 0 form with a spacing hetween pleated sheets (dool) of 9.03 A, termed 61. If the heating was carried out a t temperatures higher than 85"C, the 01 form underwent another conformational transition reducing the dool value from 9.03 to 7.83 A (termed 0 2 ) without any prominent change in the fiber repeat distance (i.e., the polypeptide backbone conformation). The time course of these two transitions was followed by measuring the infrared spectra of the samples, and it was concluded that the a -01 transition in its initial stage obeys a pseudo-first order rate process with activation enthalpy and entropy of 54 kcal/mol and 92 eu, respectively. On the other hand, the typical sigmoidal conversion curves observed for the transition between the two types of 0 forms (01 -02) indicate that this transition proceeds via a socalled "nucleation and growth" process. The kinetic theory of phase transitions developed by Avrami can be applied with success to explain this transition. The infrared spectra, in the region from 1800 to 200 cm-', were measured for these two @ forms and the results showed that the conformation of the side chains and the mode of the hydrogen bonding between the side-chain carboxyl groups undergo appreciable change during the transition.The heat-induced conformational transition of p o l y (~-G I u~* L-VaP) was also studied. The copolymer was transformed from the a-helical conformation directly to the 0 2 form. The reason for this was thought to be due to the fact that the L-valine residues and the Lglutamyl residues near the L-valine residues have a strong tendency to take the more compact (32 form. INTRODUCTIONIt is well known that in aqueous solution poly(L-glutamic acid) [poly-(Glu)] undergoes a reversible helix-coil transition.' The random coil exists a t neutral and high pH, where the glutamyl side chains are negatively charged, and can be transformed to the a-helix by reducing the pH a t room temperature. Poly(G1u) in the a-helical conformation exhibits a strong tendency to form an associated state. An unusual be-* Publication 1043 of the Graduate Department of Biochemistry, Brandeis University.Present address: Department of Chemistry, School of Science and Engineering, WaJohn Simon Guggenheim Fellow seda University, Shinjuku-ku, Tokyo 160, Japan. 1974-1975 tt To whom correspondence should be addressed. 420ITOH, FOXMAN, AND FASMAN havior of the titration curve (a hysteresis) in the low-pH region of this polymer has been attributed to this association.24 The associationdissociation reaction of a-helical poly(G1u) in aqueous solution was also studied by measuring the temperature dependence of the Moffitt-Yang parameter a0 and by means of light ~cattering.~ These papers, however, did not consider the possibility that the secondary structure of the polypeptide ...

SynopsisRaman spectra were measured for poly (L-histidine) in HzO, in D20, L-histidine in HzO, L-histidine-d3 (and d4) in DzO, and 4-methylimidazole in H20 with various pH (or pD) values. The Raman scattering peaks observed for these samples were ascribed to the neutral and positively charged imidazole groups on the basis of the spectral changes due to the pH variation and to the deuterium substitution of the imino protons. The vihrational modes of these peaks were deduced from the normal coordinate analysis made on the positively charged and neutral 4-ethylimidazoles. The Raman scattering peaks from the imidazole groups in the neutral form clearly indicate that these imidazole groups exist in the equilibrium between the two tautomeric forms, the 1-N protonated form (tautomer I) and the 3-N protonated one (tautomer 11). For example, the breathing vibration of the 1-N protonated form is observed a t 1282 cm-' for L-histidine and a t 1304 cm-' for 4-methylimidazole, while the breathing vibration of the 3-N protonated form is observed a t 1260 cm-' for I>-histidine and 4-methylimidazole. From the temperature dependence of the relative intensities of the tautomer I peak to that of the tautomer 11, it was concluded that the tautomer I is energetically more stable than the tautomer 11, and the AH value is 1.0 f 0.3 kcal/mol for L-histidine and 0.4 f 0.1 kcal/mol for 4-methylimidazole. Poly(L-histidine) with the neutral imidazole side chains shows the amide I peak at 1672 cm-', indicating that the sample assumes the antiparallel pleated-sheet structure. P o l y (~-A l a~~~-H i s~~) and p o l y (~-A l a "~~-H i s "~)were found to take the @-helical and P-form conformations, respectively.

Sum frequency generation (SFG) spectra and surface pressure-molecular area (pi-A) isotherms have been obtained for mixed cholesterol-DPPC monolayers with cholesterol mole fractions, x(chol.), from 0 to 1.0, at the air-water interface, under same conditions, at 22 degrees C. Analysis of the spectra indicated that incorporation of cholesterol into the monolayers at 3 mN m-1 greatly increases the conformational and orientational order of the alkyl chains of DPPC, maximizing these properties at x(chol.)=0.4. Analysis also indicated that order in the mixed monolayers at 15 and 35 mN m-1 is not affected by incorporation of cholesterol. The pi-A isotherms measured at 3 mN m-1 for the mixed monolayer with x(chol.)=0.4 have the largest negative deviation of the molecular area relative to those of ideal mixtures (the so-called "condensation effect" of cholesterol), indicating the most thermodynamically stable state. Comparison of results from SFG spectra and pi-A isotherms explicitly proved that the condensation effect can be interpreted in terms of conformational and orientational ordering of the alkyl chains of DPPC.

Absorption, infrared reflection absorption (IRA), and resonance Raman scattering (RRS) spectroscopies were applied to obtain direct information about the conformation change of a polydiacetylene (abbreviated to PDA) produced by UV irradiation of the Langmuir−Blodgett (LB) films of the cadmium salt of a diacetylene derivative, 10,12-pentacosadiynoic acid (DA), with the number of monolayers from 1 to 31. The rate and extent of the polymerization of DA monitored by the relative intensity change of the IRA bands due to C⋮C stretching vibrations were correlated with orientation changes of the alkyl groups of DA and changes in the conjugation length of the PDA backbone elucidated by RRS spectra in the C⋮C stretching vibration region. The results proved the following mechanism of the conversion from a blue (λmax ≈ 635 nm) to a red phase (λmax ≈ 540 nm) during the polymerization of DA. The conversion proceeds through two steps. The polymerization reaction itself is almost completed in the first step, although a residual reaction may take place in the second step. During the first step the plane formed by the all-trans zigzag backbone of the alkyl groups changes its arrangement in the following way:  the orientation of the long axis of the alkyl backbone changes from a tilted state to a less tilted one, keeping the axis perpendicular to the long axis within the plane parallel to the substrate surface. This orientation change conforms to an increase in the interlayer spacing of the LB films of long-chain diacetylene monocarboxylic acids during their photopolymerization process observed through a small angle X-ray diffraction technique (Lieser, G.; et al. Thin Solid Films (1980, 68, 77). During the first step the PDA backbone keeps a fully extended conformation without any interruption of its conjugation, and the formation of the blue phase proceeds. When the polymerization proceeds to the second step, the regular plane of the all-trans alkyl group is converted to an irregular one containing gauche conformations. This conversion causes an interruption of the fully extended backbone structure and a reduction of the average conjugation length, resulting in the formation of the red phase.