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Showing papers on "Circular dichroism published in 1976"


Journal ArticleDOI
05 Feb 1976-Nature
TL;DR: X-ray analysis, circular dichroism, receptor binding and biological potencies of chemically modified insulins suggest that the conformation of the insulin molecule is critical to the formation of both the zinc insulin hexamer and the insulin–receptor complex.
Abstract: X-ray analysis, circular dichroism, receptor binding and biological potencies of chemically modified insulins suggest that the conformation of the insulin molecule is critical to the formation of both the zinc insulin hexamer and the insulin–receptor complex. Results are consistent with an insulin receptor-binding region including many of the hydrophobic residues important to dimerisation in addition to more polar surface residues. There is a further possibility of formation of an antiparallel sheet structure between the insulin and receptor molecules in the complex similar to that between monomers in the insulin dimer.

390 citations


Journal ArticleDOI
TL;DR: Results presented here suggest that the acid form is produced as an intermediate in the first stage of total unfolding at neutral pH, which may cause a difference in dynamic character in the native state between the two proteins and thus provide a reasonable interpretation for their known differences in chemical reactivity.

237 citations


Journal ArticleDOI
TL;DR: Even though some of the protein--sodium dodecyl sulfate complexes have helical contents as high as 50%, their overall conformation more closely approximates that of a random coil than a rod.
Abstract: Circular dichroism spectra have been obtained for albumin, alpha-chymotrypsinogen, collagen, concanavalin A, elastase, hemoglobin, histone f2b, alpha-lactalbumin, lactate dehydrogenase, beta-lactoglobulin, lysozyme, myoglobin, papain, ribonuclease A, and thermolysin in the presence of sodium dodecyl sulfate and dithiothreitol. While all spectra have the shape anticipated for a mixture of random coil and alpha helix, the intensities differ markedly ([theta]222 ranges from --1400 to --15 000 deg cm2/dmol). The variation in the circular dichroism can be quantitatively explained by a model which assumes that the arginyl, histidyl, and lysyl residues have an enhanced probability of propagating a helical segment in the presence of the detergent. The model also permits the computation of dimensional properties (unperturbed end-to-end distance and radius of gyration) for polypeptides of known amino acid sequence. Such computations have been performed for 67 proteins. The computed dimensions are compatible with experimental values and with the molecular weight dependence of the transport properties of the complexes. Furthermore, the model can account for the abnormal transport properties of the sodium dodecyl sulfate complexes formed by ribonuclease A, collagen fragments, and histones f2a1, f2a2, f2b, and f3. Even though some of the protein--sodium dodecyl sulfate complexes have helical contents as high as 50%, their overall conformation more closely approximates that of a random coil than a rod.

231 citations


Journal ArticleDOI
TL;DR: It is observed that strength of binding, ease of dissociation of DNA-anthracycline complexes, and the degree of inhibition of the DNA-dependent RNA polymerase are dependent on the presence of the amino sugar moiety of daunoseamine.
Abstract: The interaction specificity of salmon sperm DNA with various derivatives of daunorubicin has been studied. The results of binding, viscometric, 1H nuclear magnetic resonance (NMR), flow dichroism, DNA template inhibition, rates of dissociation, and circular dichroism studies are found to be consistent with an intercalation mode of binding of the anthracycline ring as has been shown by other investigators. Moreover, it is observed that (i) strength of binding, (ii) the ease of dissociation of DNA-anthracycline complexes, and (iii) the degree of inhibition of the DNA-dependent RNA polymerase are dependent on the presence of the amino sugar moiety of daunoseamine. The results are consistent with specific H bonding of the amino group of the sugar moiety with DNA as has been suggested earlier by Pigram et al. (Pigram, W.J., Fuller, W., and Hamilton, L.D. (1972), Nature (London), New Biol. 235, 17). Peptide derivatives substituted at the amino sugar function of daunorubicin lower the affinity of the drug to DNA and presumably interfere with the "full insertion" of the anthracycline drugs between base pairs of DNA. The significance of these findings in relation to the biological efficacy of daunorubicin and related derivatives as antileukemic agents is discussed.

182 citations



Journal ArticleDOI
TL;DR: Spectroscopic studies of the blue copper proteins Rhus vernicifera stellacyanin, bean plastocyanin, and Pseudomonas aeruginosa azurin have been made, finding low energy bands attributable to the d-d transitions 2B2 leads to 2E and 2B1 in a flattened tetrahedral copper-(II) center.
Abstract: Low temperature absorption, circular dichroism, and magnetic circular dichroism spectral studies of the blue copper proteins Rhus vernicifera stellacyanin, bean plastocyanin, and Pseudomonas aeruginosa azurin have been made. Low energy bands attributable to the d-d transitions 2B2 leads to 2E and 2B2 leads to 2B1 in a flattened tetrahedral (D 2d) copper-(II) center are observed in these proteins at about 5000 and 10,000 cm-1, respectively. The band positions accord well with ligand field calculations based on a tetrahedral structure that is distorted approximately 6 degrees toward a square plane. The ligands in this flattened tetrahedral coordination unit in bean plastocyanin are identified from various spectroscopic experiments as His-38, Cys-85, His-88, and a deprotonated peptide nitrogen (N) a few residues above His-38.

126 citations


Journal ArticleDOI
TL;DR: Ultraviolet and infrared spectroscopy, circular dichroism in various solvents and in particular 13C nuclear magnetic resonance have been used for a comparative study of suzukacillin with alamethicin.

110 citations


Journal ArticleDOI
TL;DR: The extended spectrum of gelatin reveals that the circular dichroism of this unordered polymer is more closely related to the spectrum of charged polypeptides than might be evident from near ultraviolet work.
Abstract: Circular dichroism spectra for acid-soluble calfskin collagen, gelatin, and poly(proline) II in solution have been extended into the vacuum ultraviolet region. The extended spectrum of gelatin reveals that the circular dichroism of this unordered polymer is more closely related to the spectrum of charged polypeptides than might be evident from near ultraviolet work. A short-wavelength band is found at about 172 nm, which corresponds in position, magnitude, and sign to a band recorded earlier for poly(L-glutamic acid) at pH 8.0. This band is observed in a helical structure for the first time in the vacuum ultraviolet circular dichroism and absorption spectra of poly(proline) II. Both circular dichroism and absorption spectra point to the assignement of this band as the nσ*. Neither the nσ* nor the expected positive lobe of the ππ* helix band is observed in the extended circular dichroism spectrum of collagen. We postulate that these two bands cancel here in analogy to the case of α-helical poly(L-glutamic acid).

104 citations


Journal ArticleDOI
TL;DR: Observations provided direct support for previous data indicating that incorporation of proline analogues such as allohydroxyproline into pro-alpha chains during procollagen biosynthesis prevents the polypeptides from becoming triple helical.

101 citations



Journal ArticleDOI
TL;DR: It has been shown by high-resolution proton magnetic resonance (PMR) spectroscopy and circular dichroism that an H2A/H2B histone complex exists after salt extraction of these histones from chromatin and that this complex can be fully renatured from both urea-denatured acid-extracted and from urea
Abstract: It has been shown by high-resolution proton magnetic resonance (PMR) spectroscopy and circular dichroism (CD) that an H2A/H2B histone complex exists after salt extraction of these histones from chromatin and that this complex can be fully renatured from both urea-denatured acid-extracted and from urea-denatured salt-extracted histones. The histone complex is shown to involve specific secondary and tertiary structure. Formation of this complex is observed to be critically dependent on pH, occurring at and above pH 5. It cannot be induced below pH 5 by increase in ionic strength. From CD spectra the H2A/H2B complex is shown to contain about 37%α helix but no β structure, the latter being confirmed by infrared spectroscopy in the 6-μm region. The PMR spectra show that the structured region includes most of the aromatic residues of both histones, at least two histidine residues of H2B and probably histidines 31 and 82 of histone H2A. The secondary structure of histones H2A and H2B is predicted using the Chou and Fasman procedure and comparisons are made between the predictions for histones of different species. These results in conjunction with the experimental evidence lead to the conclusion that at least residues 31–95 of H2A and residues 37–114 of H2B, i.e. the more apolar regions of the molecules, are involved in the tertiary structure of the H2A/H2B complex.

Journal ArticleDOI
29 Jan 1976-Nature
TL;DR: The results of circular dichroism (CD) studies strongly suggest that the protein has a quite different conformation in its membrane-bound state, so that a major conformational change must accompany incorporation into the virus.
Abstract: RECENT structural studies1,2 indicate that the DNA of filamentous bacteriophages is enclosed in a sheath of α-helical coat protein. In the course of phage biosynthesis this protein is tightly bound to the membrane of the host (Escherichia coli)3,4. We present here the results of circular dichroism (CD) studies strongly suggesting that the protein has a quite different conformation in its membrane-bound state, so that a major conformational change must accompany incorporation into the virus.

Journal Article
TL;DR: The spectral properties of Fc could not be fully accounted for on the basis of the spectra observed for the isolated domains which suggested that inter-domain interaction might be significant in Fc.
Abstract: Exposure of Fc fragments derived from human IgG1 myeloma proteins to acid pH rendered the region between the Cgamma2 and Cgamma3 domains transiently susceptible to cleavage by trypsin upon return to neutral pH. Trypsin covalently linked to Sepharose was used and two fragments derived from the Cgamma2 region and one from the Cgamma3 region were purified by column chromatography. On the basis of amino acid analysis, primary sequency data, antigenic properties, and m.w., one of the Cgamma2 fragments was shown to consist of two polypeptide chains of unequal mass joined by the inter-heavy chain disulfide bonds. The larger chain corresponded to a stretch of gamma-chain between Thr 223 and Lys 338 (Eu numbering) and the shorter chain to the section between Thr 223 and Lys 248. The other Cgamma2-fragment was a disulfide-linked dimer of the Thr 223 to Lys 338 sections of the paired gamma-chains. When this latter fragment was reduced under mild conditions it dissociated into monomers indicating that there was little or no noncovalent interactions between the Cgamma2 domains. The Cgamma3-fragment was shown to be a noncovalent dimer composed of the Glu 345 to Lys 349 sections of the two gamma-chains although some heterogeneity was apparent at the amino-terminus. Circular dichroism was used to probe the conformational relationships between the isolated domains and the parent Fc. The spectral properties of Fc could not be fully accounted for on the basis of the spectra observed for the isolated domains which suggested that inter-domain interaction might be significant in Fc.

Journal ArticleDOI
TL;DR: The macromolecular structure (protein-protein interaction which may result in the possible exciton interaction of the retinal pi-pi* (NV1) transition moments and protein-lipid interaction) are not significantly altered and the interaction between the apoprotein and retinal seems to be relatively more pronounced than the 13-cis form.

Journal ArticleDOI
TL;DR: It appears that mouse submaxillary epidermal growth factor and these modified forms contain a stable (and similar) tertiary structure, compared to several proteins two to four times its size.
Abstract: Mouse submaxillary epidermal growth factor (EGF) is a 53-residue single chain peptide hormone of known amino acid sequence which contains three disulfides, five tyrosines, and two tryptophans. Circular dichroic (CD) spectra have been obtained and resolved for EGF, several well-characterized chemical and enzymic derivatives, and related low molecular weight model compounds. Assignments have been made to most of the resolved bands; these include the peptide, aromatic, and disulfide chromophores. From a comparison of the rotational strength of the 213-nm resolved CD band in native EGF with that of standard proteins, EGF is estimated to contain about 22% beta structure and no alpha helicity. A derivative of EGF lacking the five carboxyl-terminal residues (prepared by limited trypsin digestion) and the cyanogen bromide derivative, in which there is a single main-chain cleavage at residue 21, have spectra properties indicative of approximately 10 and 12% beta structure, respectively. The near-ultraviolet CD spectra of the derivatives are similar to, albeit not identical with, that of EGF. The rotational strengths characteristic of the side-chain chromophores in EGF and these derivatives are several-fold higher than the corresponding values in low molecular weight model compounds. Thus, it appears that EGF and these modified forms contain a stable (and similar) tertiary structure. In contrast, the S-aminoethylated derivative of EGF exhibits a drastically altered CD spectrum relative to EGF indicating a different conformation(s). Equilibrium studies on the guanidinium hydrochloride (GdmCl) mediated reversible unfolding of EGF showed that the transition midpoint is quite high (i.e., 6.89 M GdmCl at 25.0 degrees C), thus, indicating considerable stability. From these data a rough estimate of 16 kcal/mol can be made for the unfolding free energy (delta G degrees) of EGF in the absence of denaturant. Interestingly, EGF exhibits greater stability characteristics than several proteins two to four times its size. The cyanogen bromide derivative of EGF exhibited greatly reduced stability characteristics, e.g., the transition midpoint occurred at 4.19 M GdmCl (25.0 degrees C) and delta G degrees was estimated to be approximately 4 kcal/mol. Thus, a single main-chain cleavage reduced the stability of EGF by about 70%. Thermal transitions of EGF and the cyanogen bromide derivative in the presence of concentrated GdmCl are characterized by a relatively high enthalpy of about 25 kcal/mol at 40 degrees C and a low (probably zero) heat capacity. From these thermodynamic parameters one can calculate that the large reduction in delta G degrees due to scission of the single peptide bond between residues 21 and 22 can be attributed almost completely to a change in entropy; e.g., at 40 degrees C the apparent entropy of unfolding of EGF is 20.4 cal mol-1 deg-1 while that of the cyanogen bromide derivative is 66.4 cal mol-1 deg-1.


Journal ArticleDOI
TL;DR: The findings suggest that the amphipathic helix is an important structural unit in lipid-associating proteins and that this unit can be recognized on the basis of its amino acid sequence.
Abstract: Polypeptide segments, composed of alpha helixes with specific surface topography termed amphipathic helixes, have been proposed as the basic lipid-associating domains of apolipoproteins from the plasma lipoproteins. A computer search for proteins having sequences that could form amphipathic helixes indicated that amyloid A, a pathologically occurring protein usually associated with "secondary" amyloidosis, also contained amphipathic helixes. In studies reported here, amyloid A is shown to associate spontaneously with phospholipid vesicles with the following results: (a) the formation of a protein-lipid complex isolated by equilibrium density gradient ultracentrifugation, (b) a 100% increase in alpha helicity as measured by circular dichroism, (c) a 9-nm shift in the fluorescence maximum due to the single tryptophan residue located in the amphipathic region, indicating the tryptophan is moving from a polar to a nonpolar environment, and (d) the formation of stacked disk-like protein-lipid complexes as visualized by negative stain electron microscopy. The temperature dependence of the circular dichroic spectrum of the amyloid A-phospholipid complex suggests that the complex is formed by insertion of protein between the fatty acyl chains of the lipid. These findings suggest that the amphipathic helix is an important structural unit in lipid-associating proteins and that this unit can be recognized on the basis of its amino acid sequence. In addition, these studies have implications for the origin and function of amyloid A protein.

Journal ArticleDOI
TL;DR: High-resolution proton magnetic resonance spectroscopy, circular dichroism, and infrared spectroscopies and ultracentrifugation studies have been carried out on the salt-extracted (H3/H4)2 tetramer from calf thymus, demonstrating that the tetramer contains some elements of tertiary structure.
Abstract: High-resolution proton magnetic resonance spectroscopy (270 MHz), circular dichroism, and infrared spectroscopies and ultracentrifugation studies have been carried out on the salt-extracted (H3/H4)2 tetramer from calf thymus. The tetramer contains about 29% alpha helix and no beta structure. It is denatured in 6 M urea but can be renatured simply by dialysis to water. The proton spectrum shows a number of perturbed resonances which are not observed in the spectra of either H3 or H4 alone. The observation of these resonances demonstrates that the tetramer contains some elements of tertiary structure. The overall appearance of the spectrum however is close to that of a partially denatured protein. Sedimentation velocity studies show the tetramer to have a frictional ratio of 1.99 in 50 mM acetate/50 mM bisulfite and thus to be hydrodynamically quite different from a globular protein. Two possible structural models compatible with the data are discussed.

Journal ArticleDOI
TL;DR: A stable, 2Fe-type ferredoxin has been prepared from Halobacterium halobium and purified by chromatography and shows much similarity to plant and algal ferredoxins, but it does not seem to mediate electron transport in the NADP-photoreduction system of chloroplasts.
Abstract: A stable, 2Fe-type ferredoxin has been prepared from Halobacterium halobium and purified by chromatography. A similar ferredoxin was also found in three other Halobacteria. The ferredoxin is present in large amounts-about 1 percent of the total soluble protein. From amino acid composition a molecular weight of 14800 +/- 200 was calculated. The ferredoxin was found to contain two atoms each of iron and sulphide. The midpoint redox potential of the protein is about -345 mV. The electron paramagnetic resonance spectrum of the reduced form shows much similarity to plant and algal ferredoxins with gx = 1.90, gy = 1.97 and gz = 2.07. The same similarity is observed in the optical absorption, optical rotatory dispersion and circular dichroism spectra. However it does not seem to mediate electron transport in the NADP-photoreduction system of chloroplasts. Extracts of the bacterial cells catalyze the reduction of the ferredoxin by NADH.



Journal ArticleDOI
TL;DR: These calculations illustrate that a large CD enhancement may accompany aggregation even in the absence of a conformation change in eith monomer, and the largest calculated contributions to tryosyl CD arise from interactions with far-ultraviolet transitions of neighboring aromatic groups.
Abstract: The tyrosyl circular dichroism (CD) has been calculated using the conformation of pig insulin observed in rhombohedral crystals containing 2 zinc atoms per hexamer. These calculations predict that the tyrosyl CD at 275 nm will be enhanced disproportionally as monomers interact to form dimers and as dimers interact to form hexamers. This enhanced tyrosyl CD (..delta..epsilon per 5800 molecular weight) results from new coupling interactions generated in the regions of contact between monomers and between dimers. These calculations illustrate that a large CD enhancement may accompany aggregation even in the absence of a conformation change in either monomer. The tyrosyl CD intensities calculated for monomers, dimers, and hexamers of 2-zinc pig insulin are compatible with the experimentally observed CD spectra which are enhanced about fourfold in the hexamer compared with the monomer. Zinc ions and other metals do not contribute directly to the tyrosyl CD but only influence the optical properties by promoting the hexameric state. The relation of the integrity of the molecule to dimer formation and the biological activity of the molecules are discussed. The largest calculated contributions to tyrosyl CD arise from interactions with far-ultraviolet transitions of neighboring aromatic groups. In the hexamer, about half of themore » tyrosyl CD intensity is calculated to arise from Tyr-A14.« less

Journal ArticleDOI
TL;DR: In salt-free solutions, each of the four major subfractions show very little change in conformation in going from low to neutral pH, but each shows a very sharp transition near pH 9.5, which gives rise to a marked increase in fluorescence anisotropy and fluorescence intensity, and involves the formation of both alpha and beta strucute in a manner similar to that of the salt-induced state.
Abstract: This paper presents the first study of conformational changes in the subfractions of calf thymus H1. H1 was fractionated by the method of Kincade and Cole (Kincade, J. M., and Cole, R.D. (1966), J. Biol. Chem. 241. 5790) using a very shallow Gdn-HC1 gradient. A possible new H1 subfraction, about 5--8% of the H1, has been found and characterized by amino acid analysis and electrophoresis. The effects of salt concentration and pH on the conformation of each of the four major subfractions have been studied by measuring the fluorescence anisotropy of the tyrosine emission and the circular dichroism (CD) of the peptide bond. Upon the addition of salt to aqueous solutions at neutral pH, all four subfractions show an instantaneous change in fluorescence anisotropy, fluorescence intensity, tyrosine absorbance, and CD. The folding associated with this instantaneous change is highly cooperative, and involves the region of the molecule containing the lone tyrosine, which becomes buried in the folded form. The folding of subfraction 3a is more sensitive to salt than the other major subfractions. Upon folding, approximately 13% of the residues of subfractions 1b and 2 form alpha and beta structure; 3a and 3b have approximately 16% of the residues in alpha and beta structures. There is no evidence for interactions between the subfractions. In salt-free solutions, each of the four major subfractions show very little change in conformation in going from low to neutral pH, but each shows a very sharp transition near pH 9. This transition gives rise to a marked increase in fluorescence anisotropy and fluorescence intensity, and involves the formation of both alpha and beta strucute in a manner similar to that of the salt-induced state.

Journal ArticleDOI
TL;DR: Avarol is the first naturally occurring sesquiter-penoid of the 9,4-friedodrimane type to be isolated as discussed by the authors, obtained from the marine sponge Disidea avara.
Abstract: With the aid of circular dichroism, n.m.r. shift reagents, and 13C n.m.r. spectroscopy the absolute stereochemistry has been assigned to avarol {2-[(1R)-1,2,3,4,4a,7,8,8aα-octahydro-1β,2β,4aβ,5-tetramethyl-1-naphthylmethyl]-hydroquinone}, obtained from the marine sponge Disidea avara. Avarol is the first naturally occurring sesquiter-penoid of the 9,4-friedodrimane type to be isolated.

Journal ArticleDOI
TL;DR: After reconstitution with adrenodoxin and its reductase, this cytochrome P-450 was highly active for cholesterol desmolase with an NADPH-generating system as electron donor but was not active for steroid 11beta-hydroxylase.

Journal ArticleDOI
TL;DR: The study of Ca+2 and Mg+2 complexes of tetracycline in buffered solution was undertaken to determine their stoichiometry and the chelation sites.

Journal ArticleDOI
TL;DR: Ribosomal 30S protein S1 causes disruption of the secondary structure of certain pyrimidine-containing polynucleotides, which are stoichiometrically converted by S1 to structures indistinguishable from their partially or completely thermally denatured forms, as revealed by circular dichroism.
Abstract: Ribosomal 30S protein S1 causes disruption of the secondary structure of certain pyrimidine-containing polynucleotides. Helical poly(U), poly(C, U), and neutral and acidic poly(C) are stoichiometrically converted by S1 to structures indistinguishable from their partially or completely thermally denatured forms, as revealed by circular dichroism. Of the several double- and triple-stranded helical polynucleotides tested that contain one polypurine strand and at least one polypyrimidine strand, only the conformation of the DNA.RNA hybrid, poly(A)-poly(dT), is perturbed. In the presence of S1, this hybrid undergoes a transition to a new structure that has a circular dichroism spectrum unlike either the native or thermally denatured forms. Intercalated ethidium bromide is released from poly(A)-poly(dT) by S1, confirming the occurrence of a conformational rearrangement. The translation inhibitor, autintricarboxylic acid, completely inhibits the action of S1 on polypyrimidines, but has no effect on the conformational perturbation of poly(A(-poly(dT). The possible relation between these observations and the biological function of protein S1 is discussed.


Journal ArticleDOI
TL;DR: In this paper, a coulombic correlation between the components of the electric hexadecapole moment of the 1 A 1→1 T 1 d-electron transition of the cobalt(III) ion in the [CoN6] chromophore and a transient electric dipole induced in each ligand group was found.
Abstract: The optical activity of the tris-diamine complexes of cobalt (III) in the visible region is accounted for quantitatively by a coulombic correlation between the components of the electric hexadecapole moment of the 1 A 1→1 T 1 d-electron transition of the cobalt(III) ion in the [CoN6] chromophore and a transient electric dipole induced in each ligand group. The correlated electric dipole of the ligand group forms a non-zero scalar product with a component of the magnetic dipole moment of the cobalt(III) ion d-electron transition in the first order employing either an O or a D 3 effective chromophoric symmetry. The calculated first-order rotational strengths account largely for the observed optical activity due to the chiral puckered conformation of the chelate rings and for the axial single-crystal circular dichroism of a cobalt(III) tris-diamine complex in a uniaxial crystal. The second-order rotational strengths improve the agreement and accommodate the observed circular dichroism of randomly-oriented co...

Journal ArticleDOI
TL;DR: A model, consistent with the results of the physicochemical studies and with semi-empirical rules for secondary structure formation, is proposed for somatostatin, which consists of a hairpin loop with several residues in an antiparallel beta-pleated sheet, is somewhat elongated, and contains a hydrophobic domain at one end and a Hydrophilic domain at the other end.
Abstract: Somatostatin is a hypothalamic tetradeca peptide that inhibits the release of growth hormone insulin, and glucagon. The circular dichroism spectrum is characterized by negative extrema at 238 nm and 270 nm, and a positive extremum at 225 nm. The far ultraviolet circular dichroism spectrum is consistent with the presence of ordered secondary structure such as beta-structure, but not alpha-helix. Sedimentation equilibrium results demonstrate that somatostatin exists in its monomeric form (i.e., a molecular weight of 1610 +/- 36 was obtained) and, thus, the structure must arise from intramolecular interactions. The diffusion constant of somatostatin was estimated to be 1.66 X 10(-6) cm2/sec. These data are consistent with an ellipsoidal rather than a spherical shape. The magnitude of the ellipticity at both 225 nm and 238 nm is quite dependent on guanidinium hydrochloride concentration; the midpoint occurs at about 3 M and the transition is cooperative-like. These data strongly suggest that somatostatin has a stable conformation in aqueous solution. A model, consistent with the results of the physicochemical studies and with semi-empirical rules for secondary structure formation, is proposed for somatostatin. The proposed structure consists of a hairpin loop with several residues in an antiparallel beta-pleated sheet, is somewhat elongated, and contains a hydrophobic domain at one end and a hydrophilic domain at the other end.