The de novo design of peptides and proteins has recently emerged as an approach for investigating protein structure and function. Designed, helical peptides provide model systems for dissecting and quantifying the multiple interactions that stabilize secondary structure formation. De novo design is also useful for exploring the features that specify the stoichiometry and stability of alpha-helical coiled coils and for defining the requirements for folding into structures that resemble native, functional proteins. The design process often occurs in a series of discrete steps. Such steps reflect the hierarchy of forces required for stabilizing tertiary structures, beginning with hydrophobic forces and adding more specific interactions as required to achieve a unique, functional protein.

Photoinitiation of relaxation of two peptides (labeled 1 and 2) and spectroscopic studies of the ensuing dynamics have led to new information about peptide conformational dynamics. Following photolysis of the aryl disulfide chromophore that constrains a peptide to be distorted from its equilibrium form, the S−S bond is broken in <200 fs, and the liberated thiyl radicals either undergo geminate recombination or diffuse apart to allow the peptides to change conformation. From anisotropy measurements, overall peptide rotation is on the time scale of 600 ps. At an even earlier time (ca. 100 ps), transient IR measurements show a bleaching of the amide I‘ region, arising from a vibrational Stark effect produced upon ring opening of peptide 2. We did not detect any significant shift in the amide I‘ region up to 2 ns, suggesting no significant helix formation in this time domain. Thiyl radicals arising from peptide 2 recombine with a power law rate over the time range from picoseconds to microseconds signaling an unusual type of scaled kinetics.

The high carrier mobility of films of semiconducting single-walled carbon nanotubes (SWNTs) is attractive for electronics applications, but the presence of metallic SWNTs leads to high off-currents in transistor applications. The method presented here, cycloaddition of fluorinated olefins, represents an effective approach toward converting the "as grown" commercial SWNT mats into high-mobility semiconducting tubes with high yield and without further need for carbon nanotube separation. Thin-film transistors, fabricated from percolating arrays of functionalized carbon nanotubes, exhibit mobilities >100 square centimeters per volt-second and on-off ratios of 100,000. This method should allow for the use of semiconducting carbon nanotubes in commercial electronic devices and provide a low-cost route to the fabrication of electronic inks.

No abstract

No abstract

The development of an optical trigger for protein folding is described. The optical trigger is an aryl disulfide embedded in a polypeptide such that the aryl disulfide constrains the peptide in a nonhelical conformation. Upon photocleavage of the SS bond, the peptide can then commence to fold into an R-helical conformation. Two thiotyrosine derivatives, (S)-4′-mercaptophenylalanine (Tty) and 3-N-(4′-mercaptophenyl)-(S)-2,3-diaminoproprionate (Aty), have been prepared and incorporated into polyalanine peptides. The ease of synthesis of protected forms of Tty and Aty amenable for solid phase synthesis, in four steps with 30% overall yield and six steps in 40% overall yield, respectively, make these attractive candidates as precursors of the optical trigger. CD and IR spectroscopy showed that the cyclic disulfide cross-linked peptides are much less helical than their linear counterparts. Following laser flash photolysis, peptide 7, which incorporates Tty, showed total recombination of the thiyl radicals within 1 ns. Peptide 16, which incorporates Aty, showed a significant amount of long-lived thiyl radicals from nanosecond to microsecond time scale. The process of recombination is hypothesized to be governed by the peptide conformation. Because of the significant amount of long-lived thiyl radicals generated from cyclic peptide 16, Aty should prove to be of general utility in the studies of protein folding on a time scale of sub-picoseconds and greater.

No abstract

Table I. Secondary Tritium Isotope Effects in E2 Reactions of ArCLTCH2X and ArCL2CH2X (L = H or D) at 50 OC reaction kHlkT k d k T ( k~l k~L i c d ' 1" + EtONafEtOH 1.204 f 0.015 1.0314 f 0.010 1.106 f 0.033 2b + t-BuOKfr-BuOH 1.191 f 0.012 1.0274 f 0.008 1.092 f 0.026 a 2-Phenylethyltrimethylammonium bromide. 2-@-Chlorophenyl)ethyl tosylate. cFrom the relation k H / k T = (kD/kT)3,z6 (ref 8 and 9).transferred hydrogen are coupled with the stretching motion of the transferred hydrogen. The calculations also predict that the tunnel correction to the secondary tritium isotope effect should be diminished when the transferred atom is deuterium rather than protium. We report here experimental evidence that this is indeed the case.The experiments were modeled after the earlier ones by using 2-arylethyl derivatives tracer labeled with tritium in the j3-position. The resulting mixture can undergo the following elimination reactions 2 k r ArCL2CH2X + When L = H , k l / k 3 = (kH/kT)sec, and when L = D, k l / k 3 = manner previously describedZ for the reactions of 2-phenylethyltrimethylammonium ion (1) with ethoxide in ethanol and 2-(pchlorophenyl)ethyl tosylate (2) with tert-butoxide in tert-butyl alcohol, both at 50 OC. The results are given in Table I.The secondary kH/kT values are both substantial.' We pointed out earlier2 that the fractionation factors of Hartshorn and Shiner6,' predict k H / k T = 1.17 at 50 'c for complete rehybridmtion. Since proton transfer is incomplete in the transition state, it is unlikely that rehybridization would be complete, so the actual contribution of rehybridization to k H / k T is probably well below 1.17. The kD/kT are very much smaller than the kH/kT and remain smaller when converted to k H / k T (last column of Table I) by the r e l a t i~n s h i p~.~ (kD/kT)sec. We determined (kH/kT)= and (kD/kT)sec in theThis relationship is obeyed by the calculated semiclassical (without tunneling) primary (error I 3.8%) and secondary (error I 1.1%) isotope effects reported in ref 4. If masses are assumed to be in the ratio of reduced masses of C-H, C-D, and C-T instead of 1:2:3, the exponent in eq 1 becomes 3.34, but an exponent of ca. 6 is required to bring our calculated and directly measured kH/kT values into agreement. Any protium in the deuteriated substrate (<2% by NMR) would make kD/kT appear too large rather than too small. Table I are larger than predicted for rehybridization and larger than the ( k H / k T ) , values calculated from (kD/kT)sx is consistent only with model calculations that include t~n n e l i n g .~ The disagreements between columns 2 and 4 of Table I also constitute violations of the rule of the geometric mean.1° The principle behind the rule is that the isotope effect for a doubly labeled species should be very close to the product of the isotope effects for the corresponding singly labeled species. In other words, the two isotopes should exert their effects independently. This statement can be expressed alge-( 5 ) We believe our previously reported (ref 2) kH/kT f...