The 55 % Solution: A Formula for Molecular Recognition in the Liquid State

Mecozzi, Sandro; Rebek, Julius

doi:10.1002/(sici)1521-3765(19980615)4:6<1016::aid-chem1016>3.0.co;2-b

Cited by 811 publications

(837 citation statements)

References 15 publications

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“…A similar calculation for L9A+IB again results in an occupation value of about 60%. These fractional occupation values agree closely with the ideal encapsulation value of 55 ± 9% reported by Rebek and coworkers (45). The cavities within the L9A and L9G structures increase in volume by about 20 Å 3 when occupied by iodobenzene (Table 2).…”

Section: Iodobenzene Bindingsupporting

confidence: 89%

Structure-Based Engineering of Internal Cavities in Coiled-Coil Peptides^,

et al. 2005

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Cavities and clefts are frequently important sites of interaction between natural enzymes or receptors with their corresponding substrate or ligand molecules and exemplify the types of molecular surfaces that would facilitate engineering artificial catalysts and receptors. Even so, structural characterizations of designed cavities are rare. To address this issue, we performed a systematic study of the structural effects of single amino acid substitutions within the hydrophobic cores of tetrameric coiled-coil peptides. Peptides containing single glycine, serine, alanine, or threonine amino acid substitutions at the buried L9, L16, L23, and I26 hydrophobic core positions of a GCN4-based sequence were synthesized and studied by solution-phase and crystallographic techniques. All peptides adopt the expected tetrameric state and contain tunnels or internal cavities ranging in size from 80 Å 3 to 370 Å 3 . Two closely-related sequences containing an L16G substitution, one of which adopts an antiparallel configuration and one of which adopts a parallel configuration, illustrate that cavities of different volumes and shapes can be engineered from identical core substitutions. Finally, we demonstrate that two of the peptides (L9G and L9A) bind the small molecule iodobenzene when present during crystallization, leaving the general peptide quaternary structure intact but altering the local peptide conformation and certain superhelical parameters. These high-resolution descriptions of varied molecular surfaces within solvent-occluded internal cavities illustrate the breadth of design space available in even closely-related peptides and offer valuable models for the engineering of de novo helical proteins.A significant challenge frustrating the de novo design of functional molecules is that of precisely constructing molecular surfaces able to suitably participate in desired molecular recognition events. Internal cavities, relatively buried clefts, and tunnels are frequently important sites of interaction between natural enzymes or receptors with their corresponding substrate or ligand molecules, and the ability to engineer such surfaces would facilitate the successful design of highly-selective artificial catalysts and receptors. Mutagenesis of natural proteins to create or alter internal cavities has been used for such purposes as redesigning † We thank the National Institutes of Health for financial support (GM52190). JER, JMAG, and LJL thank the Wellcome Trust (061454/ Z/00/Z), the Spanish MCYT, and NSF, respectively, for fellowships. § Coordinates have been deposited in the RCSB Protein Data Bank: GCN4-pLI, 1UO2; L9G, 1UO3; L9S, 1UNU; L9A, 1UNT; L9T, 1UNV; L9G+IB, 1UO4; L9A+IB, 1UO5; L23G, 1UNW; L23S 1UNX; I26G, 1UNY; I26S, 1UNZ; I26A, 1UN0; I26T, 1UN1; L16G E20C, 1W5I; L16G E20C Y17H, 2BNI.* Address correspondence to this author. (858) 784-2700 (phone); (858) 784-2798 (fax); ghadiri@scripps.edu (e-mail).. 1 Abbreviations: CD, circular dichroism; SEC, size exclusion chromatography; ABA, acetamidobenzoic acid; MW,...

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Section: Iodobenzene Bindingsupporting

confidence: 89%

Structure-Based Engineering of Internal Cavities in Coiled-Coil Peptides^,

et al. 2005

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“…[21] Although this is significantly lower than the optimal 55 % packing efficiency, [22] it is in excellent agreement with thẽ 43 % occupancy recently calculated for the eight benzene guest molecules observed within the resorcin [4]arene/water Archimedean snub cube. [10] We have shown that a small structural variation-in this case the extension of an alkyl chain by one carbon atom-in the pyrogallol [4]arenes can have profound effects on the crystal packing and interactions between nanocapsules.…”

supporting

confidence: 82%

Inner Core Structure Responds to Communication between Nanocapsule Walls

et al. 2004

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“…E-mail: jrebek@scripps. each) occupy Ϸ52% of the capsule's space (420 Å 3 ), and the capsule is optimally filled (10).…”

Section: Resultsmentioning

confidence: 80%

Stereochemistry in self-assembled encapsulation complexes: Constellational isomerism

Yamanaka

Shivanyuk

Rebek

2004

Proc. Natl. Acad. Sci. U.S.A.

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A previously uncharacterized form of stereochemistry, constellational isomerism, is described. The isomerism arises from different arrangements of small-molecule guests in the space of a selfassembled, cylindrical host. The cylindrical host detains three molecules each of CHCl3, 1,2-dichloroethane, or isopropyl chloride. The exchange of guests in and out of the host is slow on the NMR time scale. The dimensions of the capsular host and the sizes of the guests hinder the mobility of molecules inside, and separate NMR signals are seen for guests at the ends of the capsule and those near its center. When two different guests are encapsulated, the spectra show up to four additional species: two sets of constellational isomers. In every pairwise combination of the three guests, all isomers could be identified. The equilibrium distributions of isomers depended on the concentrations of the guests in the bulk solution. The relative stability of the constellational isomers was a function of the polarity of the guest molecule and its ability to interact with the components of the capsule. The different arrangements represent information, and some possibilities for their use in data storage are proposed.T he stereochemistry of covalent bonds is older than a century, whereas that of mechanical bonds is younger than a decade. Carcerands (1) and catenanes (2, 3), for example, have been devised to show new forms of isomerism based on slowed molecular rotations and tumbling. Certain rotaxane (4, 5) isomers can interconvert through localized molecular translation. Weaker, intermolecular forces also can be recruited to restrain the motion, however temporarily, of molecules completely surrounded by other molecules. Reversibly formed capsules provide mechanical barriers to the tumbling of molecules detained within them; the energies separating isomers are modest but large enough to detect isomerism at ambient temperatures by NMR methods (for the preliminary communication see ref. 6). Here we develop a previously uncharacterized type of stereochemistry arising from the limited mobility of three molecules inside a cylindrical capsule (Fig. 1). Different arrangements exist for molecules in a well defined space, and we have proposed the term constellational isomerism to describe the phenomenon (7). Experimental MethodsGeneral. 1 H NMR spectra were recorded on Bruker (Billerica, MA) DRX-600 (600 MHz) or DRX-800 (800 MHz) spectrometers using the solvent signals as internal references. The energyminimized structures were calculated with HYPERCHEM 7 (MMϩ force field).Titration. Isopropyl chloride (IPC) (300 l) was added to a suspension of cylindrical capsule (3.0 mM) in mesitylene-d 12 .The appropriate volume of 1,2-dichloroethane (DCE)-d 4 was titrated into the solution, and the 1 H NMR spectrum was recorded at 273 K. The spectrum revealed IPCs in the capsule (arrays 13-17). The same titration using IPC-d 7 and DCE showed DCE at the end of the capsule (arrays 14 and 16-18). The identity of each array was conformed by titrations and revers...

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The 55 % Solution: A Formula for Molecular Recognition in the Liquid State

Cited by 811 publications

References 15 publications

Structure-Based Engineering of Internal Cavities in Coiled-Coil Peptides^,

Structure-Based Engineering of Internal Cavities in Coiled-Coil Peptides^,

Inner Core Structure Responds to Communication between Nanocapsule Walls

Stereochemistry in self-assembled encapsulation complexes: Constellational isomerism

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The 55 % Solution: A Formula for Molecular Recognition in the Liquid State

Cited by 811 publications

References 15 publications

Structure-Based Engineering of Internal Cavities in Coiled-Coil Peptides,

Structure-Based Engineering of Internal Cavities in Coiled-Coil Peptides,

Inner Core Structure Responds to Communication between Nanocapsule Walls

Stereochemistry in self-assembled encapsulation complexes: Constellational isomerism

Contact Info

Product

Resources

About

Structure-Based Engineering of Internal Cavities in Coiled-Coil Peptides^,

Structure-Based Engineering of Internal Cavities in Coiled-Coil Peptides^,