Molecular recognition

(cell and molecular biology) The ability of biological and chemical systems to distinguish between molecules and regulate behavior accordingly.
(chemistry) The (molecular) storage and the (supramolecular) retrieval and processing of molecular structural information and interactions.

The ability of biological and chemical systems to distinguish between molecules and regulate behavior accordingly. How molecules fit together is fundamental in disciplines such as biochemistry, medicinal chemistry, materials science, and separation science. A good deal of effort has been expended in trying to evaluate the underlying intermolecular forces. The weak forces that act over short distances (hydrogen bonds, van der Waals interactions, and aryl stacking) provide most of the selectivity observed in biological chemistry and permit molecular recognition. The recognition event initiates behavior such as replication in nucleic acids, immune response in antibodies, signal transduction in receptors, and regulation in enzymes. Most studies of recognition in organic chemistry have been inspired by these biological phenomena. It has been the task of bioorganic chemistry to develop systems capable of such complex behavior with molecules that are comprehensible and manageable in size, that is, with model systems. See also Enzyme; Hydrogen bond; Intermolecular forces; Nucleic acid.

The advantage of cyclic structures lies in their ability to restrict conformation or flexibility. A rigid matrix of binding sites, that is, preorganized sites, is usually associated with high selectivity in binding. A flexible matrix tends to accept several binding partners. Although sacrificing selectivity, this has the advantage of transmitting conformational information and is relevant to biological signaling events. See also Conformational analysis.

Macrocyclic (crown) ethers can bind and transport ions and imitate biological processes involving macrolides. Large ring structures that are lined with oxygen present an inner surface which is complementary to the spherical outer surface of positively charged ions.

Cyclophane-type structures offer considerable rigidity because of the aromatic nuclei. Binding forces between host and guest are largely hydrophobic. A typical system is a cyclophane-naphthalene complex (1), in which a naphthalene guest is bound by a water-soluble cyclophane derivative. Other macrocyclic structures include the cyclodextrins and hybrid structures assembled from macrocyclic subunits. See also Aromatic hydrocarbon; Coordination complexes.

Because the encircling of larger, more complex molecules with macrocycles poses structural problems, other molecular shapes have been explored. Cleft molecules offer advantages in this regard. The principle underlying these systems involves the shape of the small organic target molecules: convex in surface and bearing functional groups that diverge from their centers. Accordingly, designing a trap for such targets requires molecules of a concave surface in which functional groups converge. This 1

Systems featuring a cleft have been developed to bind adenine derivatives and other heterocyclic systems through chelation, as shown in (2). 2

Apart from the abstract questions concerning articulation of molecules, some practical applications in the pharmaceutical industry may be envisioned. Many of the target structures are biologically active, and the use of synthetic sequestering agents for metabolic substrates can represent a novel approach to biochemical methods and drug delivery.

Crystal structure of a short peptide L-Lys-D-Ala-D-Ala (bacterial cell wall precursor) bound to the antibiotic vancomycin through hydrogen bonds^[1]

Crystal structure of two isophthalic acids bound to a host molecule through hydrogen bonds^[2]

Static recognition between a single guest and a single host binding site. In dynamic recognition binding the first guest at the first binding site induces a conformation change that affects the association constant of the second guest at the second binding site. In this case it is positive allosteric system.

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The term molecular recognition refers to the specific interaction between two or more molecules through noncovalent bonding such as hydrogen bonding, metal coordination, hydrophobic forces, van der Waals forces, pi-pi interactions, electrostatic and/or electromagnetic^[3] effects. The host and guest involved in molecular recognition exhibit molecular complementarity.^[4][5]

Contents 1 Biological systems 2 Supramolecular systems 3 Static vs. dynamic 4 See also 5 References 6 External links

Biological systems

Molecular recognition plays an important role in biological systems and is observed in between receptor-ligand, antigen-antibody, DNA-protein, sugar-lectin, RNA-ribosome, etc. An important example of molecular recognition is the antibiotic vancomycin that selectively binds with the peptides with terminal D-alanyl-D-alanine in bacterial cells through five hydrogen bonds. The vancomycin is lethal to the bacteria since once it has bound to these particular peptides they are unable to be used to construct the bacteria’s cell wall.

Supramolecular systems

Chemists have demonstrated that artificial supramolecular systems can be designed that exhibit molecular recognition. One of the earliest examples of such a system are crown ethers which are capable of selectively binding specific cations. However, a number of artificial systems have since been established.

Static vs. dynamic

Molecular recognition can be subdivided into static molecular recognition and dynamic molecular recognition. Static molecular recognition is likened to the interaction between a key and a keyhole; it is a 1:1 type complexation reaction between a host molecule and a guest molecule to form a host-guest complex. To achieve advanced static molecular recognition, it is necessary to make recognition sites that are specific for guest molecules.

In the case of dynamic molecular recognition the binding of the first guest to the first binding site of a host affects the association constant of a second guest with a second binding site.^[6] In the case of positive allosteric systems the binding of the first guest increases the association constant of the second guest. While for negative allosteric systems the binding of the first guest decreases the association constant with the second. The dynamic nature of this type of molecular recognition is particularly important since it provides a mechanism to regulate binding in biological systems. Dynamic molecular recognition is also being studied for application in highly functional chemical sensors and molecular devices.

See also

• Journal of Molecular Recognition

References

1. ^ Knox, James R.; Pratt, R. F. (July 1990). "Different modes of vancomycin and D-alanyl-D-alanine peptidase binding to cell wall peptide and a possible role for the vancomycin resistance protein" (Free full text). Antimicrobial agents and chemotherapy 34 (7): 1342–7. doi:10.1128/AAC.. PMID 2386365. http://aac.asm.org/cgi/reprint/34/7/1342. 
2. ^ Bielawski, Christopher; Chen, Yuan-Shek; Zhang, Peng; Prest, Peggy-Jean; Moore, Jeffrey S. (1998). "A modular approach to constructing multi-site receptors for isophthalic acid" (Free full text). Chemical Communications: 1313–4. doi:10.1039/a707262g. http://www.rsc.org/delivery/_ArticleLinking/DisplayArticleForFree.cfm?doi=a707262g&JournalCode=CC. 
3. ^ Cosic, I (1994). "Macromolecular bioactivity: is it resonant interaction between macromolecules?—theory and applications". IEEE transactions on bio-medical engineering 41 (12): 1101–14. doi:10.1109/10.335859. PMID 7851912. 
4. ^ Lehn, Jean-Marie (1995). Supramolecular Chemistry. Weinheim: Wiley-VCH. ISBN 978-3-527-29312-4. OCLC 315928178. ^{[page needed]}
5. ^ Gellman, Samuel H. (1997). "Introduction: Molecular Recognition". Chemical reviews 97 (5): 1231–1232. doi:10.1021/cr970328j. PMID 11851448. 
6. ^ Shinkai, Seiji; Ikeda, Masato; Sugasaki, Atsushi; Takeuchi, Masayuki (2001). "Positive allosteric systems designed on dynamic supramolecular scaffolds: toward switching and amplification of guest affinity and selectivity". Accounts of chemical research 34 (6): 494–503. doi:10.1021/ar000177y. PMID 11412086. 

External links

• http://www.mdpi.org/ijms/specialissues/molecular-recognition.htm^{[dead link]} Special Issue on Molecular Recognition in the Int. J. Mol. Sci.

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