Molecular recognition and catalysis. Acceleration of phosphodiester cleavage by a simple hydrogen-bonding receptor

Jubian, Vrej; Dixon, Robert P.; Hamilton, Andrew D.

doi:10.1021/ja00029a068

Cited by 148 publications

(52 citation statements)

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“…The host molecule 59 is rigidized by intramolecular H bonds so that four guanidinum protons are directed to the interior of the cleft. The binding sites are not only well positioned to strongly bind diphenyl phosphate in CD3CN [86], they may also stabilize trigonal-bipyramidal intermediates [87] which are formed in the course of phosphoester hydrolysis [88]. Thus, an excess of 59 in the presence of lutidine as a general base markedly increased the rate constant of the cleavage of phosphoester salts in acetonitrile.…”

mentioning

confidence: 96%

Molecular recognition of organic acids and anions — Receptor models for carboxylates, amino acids, and nucleotides

Seel

Galán

Mendoza

1995

Topics in Current Chemistry

103

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mentioning

confidence: 96%

Molecular recognition of organic acids and anions — Receptor models for carboxylates, amino acids, and nucleotides

Seel

Galán

Mendoza

1995

Topics in Current Chemistry

103

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“…For example, a guanidino group is used to bind phosphoryl groups by the HIV-1 Tat protein18 and by artificial receptors. 19 Further, in Staphylococcal nuclease and ribonucleases of the T1 family, an arginine appears to play the role of K41 in RNase A. 20 We have replaced K41 with an arginine residue and an Sacetamidino residue, which is a short analog of arginine.…”

Section: Structural Implicationsmentioning

confidence: 99%

Ribonuclease A: Revealing Structure-Function Relationships with Semisynthesis

Messmore¹,

Fuchs²,

Raines³

1995

J. Am. Chem. Soc.

116

133

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Bovine pancreatic ribonuclease A (RNase A) catalyzes the cleavage of P-O 5′ bonds in RNA. Structural analyses had suggested that the active-site lysine residue (K41) may interact preferentially with the transition state for covalent bond cleavage, thus facilitating catalysis. Here, site-directed mutagenesis and semisynthesis were combined to probe the role of K41 in the catalysis of RNA cleavage. Recombinant DNA techniques were used to replace K41 with an arginine residue (K41R) and with a cysteine residue (K41C), which had the only sulfhydryl group in the native protein. The value of k cat /K m for cleavage of poly(C) by K41C RNase was 10 5 -fold lower than that by the wild-type enzyme. The sulfhydryl group of K41C RNase A was alkylated with 5 different haloalkylamines. The value of k cat /K m for the resulting semisynthetic enzymes and K41R RNase A were correlated inversely with the values of pK a for the side chain of residue 41. Further, no significant catalytic advantage was gained by side chains that could donate a second hydrogen bond. These results indicate that residue 41 donates a single hydrogen bond to the ratelimiting transition state during catalysis.

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“…Figure 6 shows the pseudo-first-order rate constants of the transesterification of 7 catalyzed by 8 alone, and 6 plus lutidine. 20 The rate enhancement imparted by 8 is between 65 and 85% of that reported for 6 and lutidine under comparable conditions. Although 8 is the dominant form of the receptor in a mixture of 6 and lutidine, it is not as efficient.…”

Section: Phosphodiester Transesterificationmentioning

confidence: 83%

“…Jubian et al 20 have demonstrated that receptor 6 in the presence of lutidine in acetonitrile can catalyze the transesterification of 7 with a rate enhancement approaching a factor of 10 3 over lutidine alone. Lutidine was used as the general base to deliver the intramolecular OH nucleophile.…”

Section: Phosphodiester Transesterificationmentioning

confidence: 98%

“…19 Bis-guanidinium receptors have been found to be successful catalysts for the transesterification of p-nitrophenyl-activated phosphodiesters, 20 the ring opening of strained cyclic phosphodiesters 21 and the cleavage of RNA under neutral conditions. 22 A thorough mechanistic understanding of the catalysis imparted in these systems is necessary for the development of future catalysts which can cleave both RNA and DNA.…”

Section: Phosphodiester Transesterificationmentioning

confidence: 99%

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NON-AQUEOUS TITRATIONS AS A TOOL IN THE STUDY OF MOLECULAR RECOGNITION PHENOMENA. USES IN DISTINGUISHING HYDROGEN BONDING FROM PROTON TRANSFER, THE MEASUREMENT OF COMPLEX INDUCED pKa SHIFTS, AND THE ABILITY TO DISTINGUISH THE CATALYTIC ROLES OF GENERAL ACIDS AND BASES

Hannon

Bell

Kelly-Rowley

et al. 1997

J. Phys. Org. Chem.

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Whenever hydrogen bonding is involved in molecular recognition, the possibility of a proton transfer from the donor to the acceptor arises. In most cases the pK a of the donor is far enough above the pK a of the conjugate acid of the acceptor for it to be clear that no proton transfer will occur. However, as the difference between the donor and acceptor pK a s decreases, it can become difficult to predict whether a proton transfer will occur. Since most hydrogen bond-driven molecular recognition is studied in low dielectric solvents, non-aqueous titrations can be used to measure the pK a s and therefore predict proton transfers. In this paper three studies which involved non-aqueous titrations are summarized. The first deals with distinguishing simple proton transfer from host-guest complex formation. The second involves measuring pK a shifts upon host-guest complex formation. The last is a study of the catalysis of a phosphoryl transfer. In all three scenarios the non-aqueous titration method gave results which would have been difficult to obtain by other means, and which proved crucial for a complete understanding of the molecular recognition process.

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Molecular recognition and catalysis. Acceleration of phosphodiester cleavage by a simple hydrogen-bonding receptor

Cited by 148 publications

References 0 publications

Molecular recognition of organic acids and anions — Receptor models for carboxylates, amino acids, and nucleotides

Molecular recognition of organic acids and anions — Receptor models for carboxylates, amino acids, and nucleotides

Ribonuclease A: Revealing Structure-Function Relationships with Semisynthesis

NON-AQUEOUS TITRATIONS AS A TOOL IN THE STUDY OF MOLECULAR RECOGNITION PHENOMENA. USES IN DISTINGUISHING HYDROGEN BONDING FROM PROTON TRANSFER, THE MEASUREMENT OF COMPLEX INDUCED pKa SHIFTS, AND THE ABILITY TO DISTINGUISH THE CATALYTIC ROLES OF GENERAL ACIDS AND BASES

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