Science and Technology Journal,
Vol. 3
Issue: 1
ISSN: 2321-3388
Aromatic Interactions in Biological Recognition Ved Prakash Singh Department of Chemistry, Physical Sciences, Mizoram University, Aizawl–796004, Mizoram, India E-mail:
[email protected] Abtract—Aromatic interactions are pivotal to biological recognition including protein-ligand interaction, DNA-ligand interaction, drug-receptor interactions etc. As about 20% amino acids are aromatic in nature, that’s why aromatic interactions have been found in a wide range of biological systems. They are playing important role for DNA helix formation, RNA recognition, and stabilization of proteins and peptides, so the role of aromatic interactions become prominent in drug receptor interactions as well as other biological
with aromatic rings in biological complexes are of paramount importance for improved drug design and lead
INTRODUCTION
interaction between molecules through non-covalent interactions interaction, and electrostatic effects.[1] The role of noncovalent interaction in nature was fully recognized only in last two decades and is of key importance in biodisciplines. host and guest involved in molecular recognition recognition plays an important role in biological systems and is observed in between receptor-ligand like antigenantibody, DNA-protein, sugar-lectin, -ribosome
These non-covalent interactions includes ionic bonds, hydrophobic interactions, aromatic interactions, hydrogen bonds and van der Waals forces like dipole-dipole, dipole induced dipole interactions etc. Non-covalent bonds are weak in nature and must therefore work together to strength is greater than the sum of the individual bonds. [6] These interactions are critical in maintaining the threedimensional structure of large molecules, such as proteins and nucleic acids.[7] The energy released in the formation of non-covalent bonds is on the order of 1-5 kcal per mole.[8]
are one of the principal non-covalent forces governing supramolecular organization and recognition processes. areas of sci.ence and molecular Engineering. They are key
These a
the vertical base stacking in DNA, and the intercalation of different drugs into DNA. These interactions are of utmost importance in drug chemistry as most of the drugs are Aromatic interactions have been utilized in materials, persed variations of electrostatic interactions.[4, 5]
10, 11]
Aromatic Interactions in Biological Recognition interaction between organic compounds containing aromatic moieties. These interactions are caused by systems, so they become stronger as the number of (A) aromatic hydrocarbons such as anthracene, triphenylene, and coronene because of the many . Waal’s interactions, plays an important role in various parts of supramolecular chemistry. There are three geometries of the benzene dimer have been modeled, parallel-displaced, T-shaped edge-to-face, and eclipsed face-to-face (Figures 1,
(B)
(C)
Fig. 2 : Edge to Face Aromatic Interaction
Moreover, supramolecular architectures, such as helices, have been constructed through stacking interactions.[16]
with a preference for the parallel displaced and T-shaped
Pioneering work by Burley and Petsko[ established the importance of edge-to-face interactions between aromatic aternary crystalline structure of peptides and proteins.
Anticancer Drug 1843U89 Bound at the Active Site of Thymidylate Synthase
CHThe interactions between arenes, alkenes, or alkynes with in chemistry and biology.[8, 17] Non-covalent interactions
molecular crystals and biological molecules. The weak
indicates that relatively weak intramolecular edge-to-
The classic hydrogen bond is one of the most important non-covalent interaction and it occurs between an aliphatic
rings can affect or determine the conformation of organic molecules in the solid state and in solution.[15, 16]
non-covalent interaction has been shown to contribute to crystal packing, stereoselectivity, protein stability
43
Singh
bond also plays a vital role in molecular recognition for numerous ligand binding proteins, carbohydrate
nicotinic acetylcholine receptor and its endogenous ligand, acetylcholine (a positively charged molecule), which binds The
conformation.[15, 19]The interaction has already been used and Trp in the acetylcholine (ACh) binding site protein (Fig. 6) shows the important contributions to the structure and function of biomolecules.[9]
Streptomyces necessary that the hydrogen atom is positioned directly
engaged in favorable interactions with one another and with
Fig. 4: Methane-Benzene Complex Show the
and Trp143 in the ACh Binding Site of an ACh-binding Protein
Tsuzuki and co-workers found that for the methanethe methane directly above the center of the benzene with one hydrogen pointed at the center of the ring, and three directed away.
molecular interaction between the face of an electron-rich (e.g. benzene, ethylene) with an adjacent cation (e.g. Li , Na ) (Fig. 5). This unusual interaction of noncovalent bonding between a monopole (cation) and a
In last of twentieth century, Egli and co-workers reported an
B-DNA are right-handed double stranded helices), despite poor base-pair stacking, is attributable to an unusual
amino acids side chain of tryptophan and tyrosine or the DNA base are capable of binding to cationic species. in stabilizing the three dimensional structure of a protein.
Benzene and a Sodium Cation 44
Stabilizing the left-handed supramolecular Structure of Z-DNA
Aromatic Interactions in Biological Recognition
for the stabilization of biological macromolecules, as well as for the binding of inhibitors in the binding pocket of biochemical receptors. Sankararamakrishnan etal have
Amaranthus caudatus (Ac-
Now it can be observed in smaller molecular host-guest
d binding can
demonstrated that such interactions between a lp donor and an aromatic acceptor can be energetically favourable.
Interactions between sulfur-containing amino acid side chains (Met, Cys) and aromatic side chains (Tyr, Trp, Phe)
contained one or more chains of alternating sulfur and
and the ammonium group on lysine (Lys) or the guanidinium group on arginine (Arg) are common in protein structures. In this case, the full positive charge on the cation is attracted to the partial negative charge on the face of the
however, the most common geometry for the interaction of of the Lys side chain into the face of the aromatic ring (Figure There are evidences that both methylated Lys and 9a) Arg are recognized via non covalent aromatic interactions. it is bound in an aromatic pocket made up of one Trp and Fig. 9b
Fig. 9: (a) Lys-Trp Pair in Typical Cation-p Geometry (b) Trimethyllysine of Histone 3A Bound to the Aromatic Pocket of the HP1 Chromodomain Sulfur–arene contacts between substrates containing aromatic amino-acid residues play an important role in the ligand-recognition function of Carbohydrate-binding
(Figure 10), methylmalonyl-CoA mutase employs an S···Ar
recognizing proteins, such as glycosidases, glycosyltransferases and lectins, aromatic amino-acid It has been suggested that the parallel stacking geometry of aromatic residues against the hydrophobic faces of carbohydrate residues was a distinctive feature in the binding of carbohydrate ligands to proteins as well as the conventional hydrogen bonding and van der Waals Fig. 10: Sulfur–arene Contacts Between Sulfur-Bearing Substrates and Their Biological Receptors 45
Singh
stacking interactions are usually associated with an offset rather than a face-to-face geometry,’ and this offset is
between two hydrophobic fragments (particularly Tyr, Phe, Trp, and Met) residues is striking.
as proteins or DNA, are probably the most relevant systems for a visual representation of non-covalent interactions, which are the main driving forces in biochemical processes for the comprehension of their three dimensional structure
Fig. 11: acyl–enzyme Complex Formation Between
(c) B-form of DNA, and the (d) A-T and (e) C-G Base Pairs
CONCLUSION The study of non-covalent interactions leads to a greater understanding of the principles governing the behaviour of chemical and biological systems. The discovery of research in biology, and these contacts are increasingly
Fig. 2: A Tight-binding Quinazoline Inhibitor Within the Active Site of TGT been known for over half a century. They control such diverse phenomena as the vertical base-base interactions which stabilize the double helical structure of DNA,’ the intercalation of drugs into DNA,’ the packing of aromatic molecules in crystal, the tertiary structures of proteins,the conformational preferences and binding properties of
interactions can be found in nucleic acids. The base-base 46
interactions are pivotal importance in materials science, crystal engineering and the intermolecular interactions involving aromatic rings in particular, are fundamental to molecular organization and recognition processes. In this review we study the non covalent interaction bond interaction, hydrophobic interaction, aromatic
weak interaction than covalent interaction or bonding but they have lots of useful application on covalent interaction
ecules are formed due to non covalent
Aromatic Interactions in Biological Recognition interaction. In medicinal chemistry a better understanding
10. with aromatic rings in chemical and biological recognition.
of new drug. Crystal engineering, protein folding, and other materialistic properties can also be investigated through the knowledge of such interactions. Utility of noncovalent interactions also seems to be involved in protein stabilization and forming synthetic receptors. There are
11. Molecular Tweezers and Clips in Chemical and Biological Systems. Accounts of chemical research. 46: 967–978.
of benzene and aromatic amino acid side chains. J. Am. Chem. Soc. 108: 7995-8001. (b) Salonen, L. M., Ellermann, M. and
intramolecular interactions among aromatic rings can play
Supramolecular chemistry is the chemistry of the intermolecular bond, covering the structures and functions of the entities formed by association of two or more chemical
14.
15. function of carbohydrate binding proteins. Protein Peptide 16.
as a supramolecular interaction by chemist. It is possible to achieve a better understanding of the contributions from arene-arene interactions in molecular recognition involving
17. pi Clouds for Noncovalent Interactions: Arenes versus Alkenes. Angew. Chem. Int. Ed. 54: 551 –555.
has become a well-established discipline in pharmaceutical very important in each and every system and become a most
18.
19.
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