Covalent biomacromolecules

The three covalent biomacromolecules share some similarities in their global structures but differ in their cellnlar functions and structural details. DNA is the carrier of genetic information, which mnst be faithfully duplicated and selectively transcribed so that each cell can synthesize the proteins it needs. RNA functions mainly in the transcription and translation of this information. In order that the nucleic acids may convey genetic information, a pattern or code must be incorporated in their chemical structure. Purine and pyrimidine bases are arranged in a definite sequence and this sequence constitutes the genetic code. 

Cemy, J. and Hobza, P. 2007. Non-covalent interactions in biomacromolecules. Phys. Chem. Chem. Phys. 9 5291-5303. 

Schematically, the two major types of reactions undergone by epoxides are rearrangements and addition of nucleophiles. Rearrangements can lead to toxic intermediates, precursors, or metabolites, whereas nucleophilic additions can lead to alkylation of biomacromolecules, i.e., formation of covalent adducts.

The photochemically induced formation of a covalent linkage between two different molecules (usually biomacromolecules) or between different moieties in the same molecule. See Photoaffinity Labeling... 

Chluba J, Voegel J-C, Decher G et al (2001) Peptide hormone covalently bound to polyelectrolytes and embedded into multilayer architectures conserving full biological activity. Biomacromolecules 2 800-805... 

The use of biomacromolecules and artificial variants thereof as hosts for homogeneous catalysts, linked by noncovalent bonds, was first implemented in the 1970s recently, this field has attracted enormous attention. The biomacromolecules are used specifically to induce chirality into catalysts for well-known reactions. Linking by noncovalent interactions is more easily achieved than linking by covalent bonding—and these interactions need not imply that the link is weak the strengths of the bonds vary enormously. For example, the avidin-biotin bond is much stronger than most supramolecular bonds considered in this context. As yet, the interest in this field is merely scientific, and applications are not anticipated in the near future. 

Figure 5.29. PAMAM dendrimer multifunctional conjugates for cancer treatment. The FA group is a folic acid cancer cell target, and FITC is fluorescein isothiocyanate, used as an imaging agent. Also shown (bottom) is the molecular structure for the anticancer drug, taxol, denoting the -OH group that covalently attaches to the dendrimer. Reproduced with permission from Majoros, I. J. Myc, A. Thomas, T Mehta, C. Baker, J. R. Biomacromolecules, 2006, 7, 572. Copyright 2006 American Chemical Society.

The transduction of chemical signals from the outside of a cell, across the cell membrane, further on into the interior of the cell, and ultimately to the cell nucleus is decisively influenced by proteins carrying covalently linked additional structural units, whose presence is vital to fulfill the designated biological functions of the biomacromolecules. To these so-called protein conjugates (Fig. 1) belong... 

Because of their electrophilic and reactive nature, arene oxides also may undergo spontaneous reactions with nucleophilic functionalities present on biomacromolecules. Such reactions lead to modified protein. DNA. and RNA structures and often cau.se dramatic alterations in how these macromoleculcs function. Much of the cytotoxicity and irreversible lesions caused by arcnc oxides are presumed to result from their covalent binding to cellular components. Several wcll-establi.shed examples of reactive arene oxides that cause serious toxicity ate presented below. 

Li, B. Haynie, D.T. Multilayer biomimetics reversible covalent stabilization of a nanostructured biofilm. Biomacromolecules 2004,5 (5), 1667-1670. 

Verheul RJ, van der Wal S et al (2010) Tailorable thiolated trimethyl chitosans for covalently stabilized nanoparticles. Biomacromolecules 11 1965-1971... 

Biomacromolecules are considered as single molecules when they are present in a well-defined stoichiometry and when they display little tendency to dissociate spontaneously under physiological conditions. This text deals specifically with covalent bio-macromolecnles in which monomer units are linked together by covalent bonds to form giant biomolecules. They include nucleic acids, proteins and polysaccharides (under this defiifition, biomembranes are excluded). The Web site of the International Union of Bio-chenfistry and Molecular Biology (lUBMB) at http //www.chem.qmw.ac.uk/iubmb/ provides useful information for the nomenclature and conformations of polynucleotides, polypeptides and polysaccharides (Figure 1.1). 

The native structures of biomacromolecules are maintained by covalent linkages of their monomer units and various noncovalent interactions between them. Therefore, these structural features (Sheeham, 2000 van Holde, Johnson and Ho, 1998) will be briefly described. 

In essence, constitutional isomers will always have different International Union of Pure and Applied Chemistry (lUPAC) names (http //www.chem.qmw.ac.uk/iupac/), whereas stereoisomers must be identified by an additional nomenclature term. Some overlap exists between configurational isomers and conformational isomers. Configurational isomers are stable under nonnal conditions whereas interconversion of conformational isomers is often rapid at room temperature. The configurations of biomacromolecules are fixed by covalent bonding. However, the conformations are highly variable and dependent on a number of factors, including the interactions between atoms in the molecule and between the molecule and its environment. The term conformation is generally used to denote secondary and tertiary structures of biomacromolecules. 

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