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Biomedical subjects

J Rebek

Publications and source records attributed to J Rebek.

10 recordsLinked to original sources
PubMed1992

Crossover reactions between synthetic replicators yield active and inactive recombinants.

Self-replicating molecules can be synthesized through the covalent linkage of two complementary subunits to give a self-complementary structure. Complementarity refers to sizes, shapes, and the weak intermolecular forces involved in molecular recognition between the two subunits. In order to provide a model system for evolution at the molecular level, "crossover" or recombination experiments were staged with synthetic replicators. These reactions gave rise to new structural types. The ability (or inability) of the new recombinants to catalyze their own formation is shown to be a consequence of their molecular shapes.

Catalysis↗
PubMed1992

Molecular recognition and self-replication.

Self-replicating molecules stand at the very boundary of chemistry with biology. This review describes the development of synthetic structures capable of self-replication from studies in molecular recognition. The weak intermolecular forces--hydrogen bonds and aromatic stacking interactions--that characterize interactions of nucleic acid components were designed into synthetic receptors for adenine. Covalent conjugates of these receptors with adenines gave self-complementary structures capable of replication. The new systems feature autocatalysis, sigmoidal product growth and even mutation. General rules for the design of replicating systems are described and these suggest that the evolution of replicating molecules was an inevitable event.

Base Composition↗
PubMed1991

Molecular recognition and the development of self-replicating systems.

Weak intermolecular forces lie at the heart of biochemical recognition phenomenon and the last decade has seen much activity in the evaluation of these forces. A number of model systems have been developed including macrocyclic structures and molecular clefts. With these structures it has been possible to measure forces at the sub-kilocalorie level involving hydrogen bonding, aromatic stacking and van der Waals interactions. This manuscript deals with molecular clefts as synthetic receptors for nucleic acid components and their ultimate use in developing chemical reactions between components within a complex. This has led to an entirely synthetic, self-replicating system that shows the features of self-complementarity and autocatalysis. A general discussion of self-replicating systems and their implications for prebiotic chemistry is developed.

DNA Replication↗
PubMed1991

Clefts as receptor and enzyme analogues.

Synthetic receptors for small biological targets have become a popular research topic in molecular recognition. This paper discusses the optimal functional group complements and the scaffolds that are ideal for such purposes. Specifically, remote steric barriers are used to control the conformation of (that is, to preorganize) hosts derived from acridine skeletons, triaryl benzenes and related systems. These structures separate entropic effects from enthalpic effects and show that entropy is an important contributor to high affinity. In a comparative study lactams are shown to be superior to imides in their capacity for self-association. Imides are shown to have higher affinity than lactams for adenine derivatives because of the presence of an unconventional hydrogen bond. Finally, preorganization in the context of chemical catalysis is demonstrated in two systems, one involving hemiacetal cleavage and a second involving a self-replicating system.

Chemical Phenomena↗
PubMed1988

Recognition and transport of adenine derivatives with synthetic receptors.

Several new synthetic agents show high affinity for binding adenine derivatives. The structures feature complementary hydrogen bonds that cause the molecular chelation of the purine nucleus. The high lipophilicity of the new agents permits the transport of adenosine and deoxyadenosine across organic liquid membranes. The use of synthetic receptors for small biological targets may have application in drug delivery.

Adenine↗
PubMed1988

Molecular recognition: model studies with convergent functional groups.

Model studies of molecular recognition are reviewed with emphasis on contributions from macrocyclic chemistry. Recent developments concerning new molecular shapes are discussed. The advantages of a molecular cleft are presented. In these structures functional groups converge to create a microenvironment complementary to substrates. Specifically, di-, tri- and tetracarboxylic acids of varying sizes are shown to recognize smaller molecules of complementary shape. The new receptors function by a combination of hydrogen bonding and aryl stacking interactions. Substrates include amines, acids, amino acids, metal ions and nucleotide components. The relationship between functional group orientation and catalysis is explored and two systems capable of concerted acid/base catalysis are introduced.

Binding Sites↗
PubMed1987

Model studies in molecular recognition.

Recognition at the molecular level is a fundamental characteristic of biochemical systems. Recent models developed in bioorganic chemistry have revealed the importance of complementarity in size, shape, and functional groups in molecular recognition. Structures that feature a cleft are particularly effective in regard to complementarity since functional groups attached to the interior of the cleft converge on substrates held inside. The molecular clefts offer the advantage of efficient construction; their surfaces can be tailored for specific applications. This article describes their use for recognition of acids, bases, amino acids, metal ions, and neutral substrates. Their ability to provide microenvironments complementary to asymmetric molecules and their future promise are discussed.

Chelating Agents↗
PubMed1975

Complement activation by a univalent hapten-antibody complex.

The univalent hapten, nonadeca lysyl epsilon-Dnp-lysine, binds tightly to rabbit anti-2,4-dinitrophenyl antibody, and the complex has a sedimentation coefficient of 6.7, characteristic of a single antibody molecule. In this communication, we show that this complex is a good activator of the serum complement system. For activation to occur, the univalent hapten must contain the specific group which binds to the antibody, and also the polycationic chain. In addition, activation requires a functional complement-binding region on the intact antibody molecule. The classical pathway appears to be involved since the first, fourth, and second components of complement are markedly depleted when the complement system is activated by this univalent hapten-antibody complex.

Animals↗
PubMed1975

Peptide synthesis with carbodiimide.

An isotope dilution assay for racemization during acid couplings is described and applied to carbodiimide-mediated synthesis. Using the coupling of t-BOC-L-phenylalamine with glycine derivatives as a model, racemization in solution falls in the 0.01 to 0.1% range and it is a function of reagent concentrations. A typical coupling using the solid phase method shows 0.03% racemate.

Carbodiimides↗