摘要:

AbstractWe report the calculated characteristics of nonnatural triplex‐forming oligonucleotide (TFO) bases recognizing base‐pair reversals (TA → AT) in a double‐helical DNA sequence. Ab initio and molecular mechanics calculations have been carried out to characterize the geometric and energetic consequences at the base‐pair reversal sites. We have estimated the free energies of solvation of the natural and proposed bases by solving the linearized Poisson–Boltzmann equation. The calculations indicate that the proposed TFO bases should bind with some specificity to the duplex. Implications of the strategy used in the context of molecular biology is discussed. © 1993 John Wil

ISSN:0006-3525    

DOI:10.1002/bip.360330902

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

年代:1993

数据来源: WILEY

摘要:

AbstractIndividual‐site isotherms for the binding of bacteriophage λ repressor to the left and right λ operators have been determined [D. F. Senear, M. Brenowitz, M. A. Shea, and G. K. Ackers (1986)Biochemistry, Vol. 25, pp. 7344–7354.] using the DNAse protection technique [ footprinting; D. J. Galas and A. Schmitz (1978)Nucleic Acids Research, Vol. 5, pp. 3157–3170]. These extensive data have been interpreted with a quantitative model that emphasized cooperative interactions between adjacently bound ligands [occupied ↔ occupied interactions; G. K. Ackers, A. D. Johnson, and M. A. Shea (1982)Proceedings of the National Academy of Science, USA, Vol. 79, pp. 1129–1133]. Overlooked in this model are the effects of cooperative interactions between a site containing a bound ligand and its neighboring unoccupied site (occupied ↔ unoccupied interactions). This paper reinterprets the existing data with a model that considers occupied ↔ unoccupied as well as occupied ↔ occupied interactions. The results yield parameters that differ substantially from those already reported. A discussion on the advisability of ignoring occupied ↔ unoccupied interactions is included. © 1993

ISSN:0006-3525    

DOI:10.1002/bip.360330903

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

年代:1993

数据来源: WILEY

摘要:

AbstractAn apolar synthetic octapeptide, Boc‐(Ala‐Aib)4‐OMe, was crystallized in the triclinic space groupP1with cell dimensionsa= 11.558 Å,b= 11.643 Å,c= 9.650 Å, α = 120.220°, β = 107.000°, γ = 90.430°,V= 1055.889 Å3,Z= 1, C34H60O11N8·H2O. The calculated crystal density was 1.217 g/cm3and the absorption coefficient ϕ was 6.1. All the intrahelical hydrogen bonds are of the 310type, but the torsion angles, ϕ and ψ, of Ala(5) and Ala(7) deviate from the standard values. The distortion of the 310‐helix at the C‐terminal half is due to accommodation of the bulky Boc group of an adjacent peptide in the nacking. A water molecule is held between the N‐terminal of one peptide and the C‐terminal of the other. The oxygen atom of water forms hydrogen bonds with N (1) ‐H and N (2) ‐H, which are not involved in the intrahelical hydrogen bonds. The hydrogen atoms of water also formed hydrogen bonds with carbonyl oxygens of the adjacent peptide molecule. On the other hand,1H‐nmr analysis revealed that the octapeptide took an α‐helical structure in a CD3CN solution. The longer peptides, Boc‐(Ala‐Aib)6‐OMe and Boc‐(Ala‐Aib)8‐OMe, were also shown to take an α‐helical structure in a CD3CN solution. An α‐helical conformation of the hexadecapeptide in the solid state was suggested by x‐ray analysis of the crystalline structure. Thus, the critical length for transition from the 310‐ to α‐

ISSN:0006-3525    

DOI:10.1002/bip.360330904

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

年代:1993

数据来源: WILEY

摘要:

AbstractUsing a sensitive birefringence instrument, the birefringence arising from the orientation of the DNA chain during electrophoretic transport has been recorded. This birefringence is shown to proceed both from the alignment (stretching) of the molecule in the direction of the electric field and from the extension of the length of its primitive path (overstretching). The contribution of these two processes can be separated in the decay of the birefringence after the end of the application of the electric field. The fast relaxation of the overstretching occurs first and is demonstrated to be the main contribution to the birefringence. The orientation factor of the remaining stretched state and its decay can be quantitatively understood using the biased reptation model. It provides, in addition, a high value for the tube diameter or gel pore sizea(4500 ± 450 Å for a 0.7% agarose gel with ac−0.6gdependence in the agarose concentrationcg) and a low value for the effective charge per base pair (0.2eas compared to 0.5eusing the condensation hypothesis). The contribution of overstretching to the birefringence is also quantitatively interpreted in term of the change in the mean lengthlof DNA inside a pore sizea. The dynamics of decay of this overstretching is well represented by a stretched exponential with a stretching exponent α = 0.44. The mean decay time decreases slightly with increasing fields and scales with the overall DNA length close toN20. © 1993 John Wiley&Sons

ISSN:0006-3525    

DOI:10.1002/bip.360330905

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe rise of the birefringence following the application of an electric field to DNA in an agarose gel has been quantitatively analyzed to demonstrate the major role played by the chain overstretching. By analyzing the field free decay after short times, we demonstrate that the overshoot is completely due to overstretching. Its time of appearance τovvaries with the field and DNA length in fair agreement with theE−lN0lnN0prediction of Lim et al. [ (1990),Journal of Chemical Physics, Vol. 92, pp. 709–721]. The τovis also the time corresponding to one tube renewal after relaxation of the overstretching. © 1993 John Wiley&Son

ISSN:0006-3525    

DOI:10.1002/bip.360330906

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

年代:1993

数据来源: WILEY

摘要:

AbstractTwotrans‐syncyclobutane photodimers of thymidylyl (3′–5′) deoxyuridine were formed by deamination of the correspondingtrans‐syncyclobutane photodimers of thymidylyl(3′–5′) deoxycytidine and were examined by1H−,13C−, and31P‐nmr spectroscopy. Correlation spectroscopy, nuclear Overhauser enhancement spectroscopy, and one‐dimensional heterodecoupling experiments allowed a more complete assignment of the1H spectra, compared with previous reports by Koning et al. [ (1991)European Journal of Biochemistry, Vol. 195, pp. 29–40] and Liu and Yang [(1978)Biochemistry, Vol. 17, pp. 4865–4876]. Deoxyribose ring conformations were calculated from1H coupling constants by pseudorotational analysis, and rotamer distributions of exocyclic bonds were calculated from the observed homonuclear and heteronuclear coupling constants. The cyclobutane ring configuration (CB) of each isomer was identified, using arguments based upon observed scalar and dipolar couplings. Glycosidic bond conformation was ascertained from nuclear Overhauser enhancements observed between base and deoxyribose protons. Isomer I (S‐type class; CB−; SYN‐ANTI) and isomer II (N‐type class; CB+; ANTI‐SYN) exhibit markedly different conformational features.31P chemical shifts and exocyclic bond rotamer distributions indicate diminished backbone flexibility for both photoproducts relative to parent thymidylyl (3′–5′) deoxyuridine. Isomer I (SYN‐ANTI) is particularly rigid, while isomer II (ANTI‐S YN) maintains some flexibility. Also,13C spectra were acquired and assigned unequivocally with the aid of short‐ and long‐range two‐dimensional heteronuclear shift

ISSN:0006-3525    

DOI:10.1002/bip.360330907

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe cyclic tetrapeptide cyclo(‐Pro1‐Ala2‐D‐Phe3‐Leu4‐) was modeled and synthesized to be used for molecular interactions and chiral discrimination studies in CDCl3. Total correlation spectroscopy and nuclear Overhauser effect spectroscopy spectra of the cyclic tetrapeptide showed the presence of one dominant stereoisomer—1—and three minor ones—2a,2b, and2c—in a relationship of 92:6:1:1. They formed three‐ to five‐hydrogen bond complexes with Boc‐D‐Ser, Boc‐L‐Ser and Boc‐L‐Thr (Boc:t‐butyloxylcarbonyl). These three Boc‐amino acids interact more strongly with2a,2b, and2cthan with1, altering their relative concentrations to 48:40:6:6. In the complex between the cyclic tetrapeptide and Boc‐D‐Ser, the stereoisomer2aexchanged chemically with1,2b, and2c, while1did not exchange with either2bor2c. This chemical exchange is due tocis‐transisomerization of the peptide bonds. The chiral discrimination of2a,2b, and2cwas stronger than that of1. No complexation occurred with Boc‐

ISSN:0006-3525    

DOI:10.1002/bip.360330908

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

年代:1993

数据来源: WILEY

摘要:

AbstractA statistical reference for RNA secondary structures with minimum free energies is computed by folding large ensembles of random RNA sequences. Four nucleotide alphabets are used: two binary alphabets, AU and GC, the biophysical AUGC and the synthetic GCXK alphabet. RNA secondary structures are made of structural elements, such as stacks, loops, joints, and free ends. Statistical properties of these elements are computed for small RNA molecules of chain lengths up to 100. The results of RNA structure statistics depend strongly on the particular alphabet chosen. The statistical reference is compared with the data derived from natural RNA molecules with similar base frequencies.Secondary structures are represented as trees. Tree editing provides a quantitative measure for the distancedt, between two structures. We compute a structure density surface as the conditional probability of two structures having distancetgiven that their sequences have distanceh. This surface indicates that the vast majority of possible minimum free energy secondary structures occur within a fairly small neighborhood of any typical (random) sequence.Correlation lengths for secondary structures in their tree representations are computed from probability densities. They are appropriate measures for the complexity of the sequence‐structure relation. The correlation length also provides a quantitative estimate for the mean sensitivity of structures to point mutations. © 1993 John Wiley&Sons, I

ISSN:0006-3525    

DOI:10.1002/bip.360330909

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

年代:1993

数据来源: WILEY

摘要:

AbstractA mathematical frame has been established to generally formulate the correlating properties of peptides. The formulation can be used to study the specificity of multisite enzymes, particularly in predicting the susceptible sites in proteins by human immunodeficiency virus (HIV) proteases, and hence can serve as a supplementary means in designing HIV protease inhibitors as potential drugs against acquired immunodeficiency syndrome. © 1993 John Wiley&Sons, Inc

ISSN:0006-3525    

DOI:10.1002/bip.360330910

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

年代:1993

数据来源: WILEY

摘要:

AbstractInteraction of a minor groove‐binding drug Hoechst‐33258, and an intercalating drug, proflavin, with the PSI (+) form of DNA, was studied using CD spectroscopy. Both drugs are shown to relax the suprahelical organization of DNA, leading to the formation of a B‐like structure, above a certain drug to phosphate ratio. However, unlike proflavin, Hoechst‐33258 brings about further structural changes after formation of the B‐like structure whereas proflavin does not. A reversal of the CD signal in the 300–450‐nm spectral region is also observed with Hoechst‐33258, indicating a change in the handedness of the suprahelical organization of DNA. To the best of our knowledge, drug‐mediated changes as presented in this paper have not been reported so far. © 1993 Jo

ISSN:0006-3525    

DOI:10.1002/bip.360330911

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

年代:1993

数据来源: WILEY