摘要:

AbstractAnalogs of Ac‐[Nle4]‐α‐MSH4–11‐NH2and Ac‐[Nle4,D‐Phe7]‐α‐MSH4–11‐NH2were prepared withD‐isomeric replacements at the His6, Arg8, and Trp9residues. The requirement for an indole moiety at position 9 also was evaluated by replacement withL‐leucine in both parent fragment analogs.D‐isomeric replacements at positions 6 and 8 in either series were detrimental to biological potency in frog (Rana pipiens) and lizard skin (Anolis carolinensis)in vitromelanotropic assays. However, Ac‐[Nle4,D‐Trp9]‐α‐MSH4–11‐NH2and Ac‐[Nle4,D‐Phe7,D‐Trp9]‐α‐MSH4–11‐NH2were equipotent and 10 × more potent than Ac‐[Nle4]‐α‐MSH4–11‐NH2, respectively, in the lizard skin bioassay, and 30 and 1900 times more potent in the frog skin bioassay. Ac‐[Nle4,D‐Phe7,D‐Trp9]‐α‐MSH4–11‐NH2was 3 × more potent than α‐MSH in the frog skin bioassay. Proton nmr studies in aqueous solution revealed a marked preservation of the backbone conformation of these linear analogs. Chemical‐shift variations due to the through‐space anisotropic influence of the core aromatic amino acid residues permitted evaluation of side‐chain topology. The observed topology was consistent with nonhydrogen‐bonded β‐like structure (ϕ = −139°, ψ = +135° forL‐amino acids; ϕ = +139°, ψ = −135° forD‐amino acids) as the predominant solution conformation. The biological and conformational data

ISSN:0006-3525    

DOI:10.1002/bip.360251102

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractThis study represents the first systematic attempt to characterize the possible sources of artifacts that can interfere with the measurement of circular intensity differential scattering (CIDS) as a function of the scattering angle. A theoretical analysis of the effect of imperfect incident circular polarizations in the measurement of baselines from nonchiral scatterers and in the signals from chiral samples is derived. From this analysis the requirements of the tolerance on the quality of the incident circular polarizations to unequivocally measure the CIDS effect are established. The protocol for alignment of the CIDS instrument and the characterization of the incident polarizations utilized in these studies are described in detail. CIDS measurements on suspensions of helical sperm cells are presented. The experimental results are modeled computationally with the use of the current CIDS theory. Good agreement between the data and the computations is obtained. The results clearly indicate the ability of CIDS to provide information on the long‐range chiral organization of samples in solutio

ISSN:0006-3525    

DOI:10.1002/bip.360251103

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractThe electronic structure of the antibiotics netropsin, distamycin A, and related compounds has been examined by various theoretical models. Calculations of both the Pariser‐Parr‐Pople (PPP) and the semiempirical CNDO/S types can account for the absorption spectrum of netropsin and distamycin A. The CD spectrum has been calculated for the conformation of netropsin found in the crystal structure of a netropsin/DNA dodecamer. Not all the CD spectral features can be attributed entirely to the chiral conformation of netropsin, indicating that there are significant interactions between netropsin and DNA. A CD calculation was also performed for distamycin A in a similar conformation. An examination of the charge‐density maps of the excited states suggests that there is substantial charge transfer from the pyrrole ring to either of the adjacent peptide linkages in these systems. At higher energies, even longer distance charge transfer can be observed. Similar behavior was seen in the monomers pyrrole‐2‐carboxamide and 3‐(formylam

ISSN:0006-3525    

DOI:10.1002/bip.360251104

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractThe equilibrium shapes of supercoiled DNA are investigated by employing an elastic model. First, a set of Euler equations is derived to determine the equilibrium shapes under ring‐closure conditions. Two exact solutions that describe circular and figure‐8 shapes are obtained. Using these and their topological properties, the configuration change from the circular to the figure‐8 form is discussed. Second, more intricate structures of supercoiling DNA are studied by a numerical analysis. Among a class of configurations, the shape that has the minimum elastic energy is explicitly determined. Poisson's ratio, the ratio of the self‐avoiding radius to the total length, and the deficit (or excess) of the linking number ΔLk are found to be the important parameters. We conclude that the topology and the elastic theory of looped DNA explain the essential features of the supercoiling p

ISSN:0006-3525    

DOI:10.1002/bip.360251105

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractThe goal of this paper is to obtain a theoretical estimate of the dielectric constant of a folded protein. To this end, we develop a form of the Kirkwood–Fröhlich dielectric theory that applies to polar solids and folded proteins. The resulting theory incorporates a factor expressing the degree to which dipolar groups are constrained within the material's structure, as well as a generalized form of Kirkwood's correlation factor. The theory is applied to a hypothetical isotropic protein composed of randomly oriented α‐helices and having a number density of dipolar groups equal to that found in actual proteins. The factor of constraint and the generalized dipole correlation factor are calculated using normal mode analysis. Temperature factors are also computed by normal mode analysis and are in reasonable agreement with those found experimentally. The computed dielectric constant is low; the best estimate is that it falls between 2.5

ISSN:0006-3525    

DOI:10.1002/bip.360251106

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractAnalogs of natural proteins have application in basic research, in medicine, and increasingly, in industry. Of the many methods developed for the fabrication of modified proteins, semisynthesis has so far been the most productive [R. E. Offord (1983)Proc. Eur. Peptide Symp., 1731–42]. The technique of fragment‐condensation semisynthesis takes as its basic raw material the native protein; fragments derived from it are manipulated by sequential degradation and resynthesis before recombination. While gene manipulation may overtake protein manipulation in general usefulness, certain types of analogs will remain accessible only by semisynthesis. Fragment condensation semisynthesis, as described above, has been used in preparing cytochromecanalogs [C. J. A. Wallace (1979)Proc. Am. Peptide Symp.6, 609–612]. To overcome the difficulty of replacing amino acids far from convenient cleavage sites, a number of variants of the method have also been used. These include fragment‐specific chemical modification [C. J. A. Wallace&K. Rose (1983)Biochem. J.215, 651–658] and solid‐phase synthesis of small [P. J. Boon, G. I. Tesser, H. H. K. Brinkhof&R. J. F. Nivard (1981)Proc. Eur. Peptide Symp.16, 127–130] or large fragments [L. E. Barstow, R. S. Young, E. Yakali, J. J. Sharp, J. C. O'Brien, P. W. Berman&H. A. Harbury (1977)Proc. Natl. Acad. Sci. USA74, 4148–4250]. The latter study gave low final recoveries, so we have prepared large peptides (38–42 residues) by classical solution methods. We have examined both their use in the reformation of the complete protein, and the physical and biochemical properties of the product analogs compared with those of th

ISSN:0006-3525    

DOI:10.1002/bip.360251107

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractThe compaction of poly[d(A–T)] · poly[d(A–T)]by Co(III) is accompanied by the formation of ψ(+)‐ and ψ(‐)‐structures. The chirality of the ψ‐structure depends on the Co(III) concentration, ionic strength, temperature, pH, and the chain length of the polymer. The two forms can be readily interconverted by manipulating these factors. Phase diagrams have been constructed that demonstrate the regions of stability of the enantiomers as a function of two variables, while other factors are held constant. At critical points in the phase diagram the two forms are in such unstable equilibrium that mechanical motion will cause ψ(+) ⇆ ψ(‐) interconversion. The formation of both ψ(+)‐ and ψ(‐)‐structures by the action of Co(III) on poly[d(A–T)] · poly[d(A–T)]contrasts markedly with the behavior of poly[d(G–C)] · poly[d(G–C)]in similar circumstances by formingonlythe ψ(+)‐structure and that of native DNA to produce no ψ at all. Thus the base sequence is important in determining the str

ISSN:0006-3525    

DOI:10.1002/bip.360251108

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

Abstract1H‐ and31P‐nmr spectroscopy have been used to investigate the self‐association of M2(5′‐CMP) [M = Li+, Na+, K+, Rb+, or (CH3)4N+; 5′‐CMP = cytidine 5′‐monophosphate], the self‐association of Li2(5′‐GMP) (5′‐GMP = guanosine 5′‐monophosphate), and the heteroassociation of 5′‐GMP and 5′‐CMP (1 : 1 mole ratio) in aqueous solution as a function of the nature of the monovalent cation. Proton spectral differences for the different 5′‐CMP salts exhibit a cation‐size dependence and have been ascribed to a change in the stacking geometry. An average stacking association constant of 0.63 ± 0.24M−1at 1°C, consistent with the weak stacking interactions of the cytosine bases, was determined for the 5′‐CMP salts. Heteroassociation of 5′‐GMP and 5′‐CMP follows the reverse of the cation order for the formation of ordered aggregates of 5′‐GMP. Heteroassociation occurs in the presence of Li+, Na+, and Rb+ions, but only self‐association occurs for the K+nucleotides. Li2(5′‐GMP), which does not form ordered species, self‐associates to for

ISSN:0006-3525    

DOI:10.1002/bip.360251109

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractUsing electric birefringence we have examined the rotational diffusion of five short DNA fragments (55 to 256 base pairs) both in polyacrylamide gels as a function of gel concentration and in solution. The length dependence of the measured rotational relaxation times in the gels is in good agreement with the prediction from the Odijk theory for the dynamics of slightly flexible rods in a network. The rotational relaxation times were found to depend on the gel concentration, contrary to the prediction from the Odijk theory. Possible reasons for this observation are discussed. The birefringence decay curves for DNA fragments in the gel were single exponential only at small electric field strength.

ISSN:0006-3525    

DOI:10.1002/bip.360251110

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractThe binding of ethidium bromide to calf thymus DNA is investigated over a wide range of temperatures and alcohol concentrations by means of fluorescence techniques. The presence of alcohol is found to lower the association constant, as isopropanol andn‐propanol are more effective than ethanol and methanol. It is also found that the data from different alcohols fall very close on the same straight line when plotted vs the solution dielectric constant ϵ. It is shown that the dependence of the binding constant on ϵ is beyond the prediction of current polyelectrolyte theories; rather, it appears that the binding is greatly controlled by the activity coefficient of the dye. The thermodynamic functions of the reaction have been estimated by means of Van't Hoff analysis: a large, negative enthalpy contributes to the binding, whereas the entropy, also favorable, is only slightly responsible for the overall free energy. Both enthalpy and entropy are strong functions of temperature and alcohol concentration. We show that the dependence of the thermodynamic quantities on the temperature is removed by considering “isodielectric” binding. This can be accomplished by a proper choice of the alcohol concentration, so that the thermal dependence of ϵ is compensated. It is found that the isodielectric free energy, enthalpy, and entropy are the same for different alcohols when plotted vs ϵ. When looking at the isodielectric quantities, it appears that the binding is now opposed by a positive enthalpy, whereas the observed favorable free energy results mainly from a large and positive entropy. The relevance of hydrophobic effects emerges from the behavior of the isodielectric thermodynamic quantities, as well as from the similarities observed when other interacting systems are

ISSN:0006-3525    

DOI:10.1002/bip.360251111

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY