Macromolecules peptide

When amino acids are linked together by acid-amide bonds, linear macromolecules (peptides) are produced. Those containing more than ca. 100 amino acid residues are described as proteins (polypeptides). Every organism contains thousands of different proteins, which have a variety of functions. At a magnification of ca. 1.5 million, the semischematic illustration shows the structures of a few intra and extracellular proteins, giving an impression of their variety. The functions of proteins can be classified as follows. 

Although quantum pharmacology calculations are more rigorous and robust when applied to small molecules, such calculations may also be applied to macromolecules. There are few drug molecules that are macromolecules peptides, such as insulin, are the exception. Usually, it is the receptor that is the macromolecule. Although receptors are discussed in detail in chapter 2, the role of quantum pharmacology in optimizing the structure of macromolecules will be presented here. 

Keywords Drug delivery Gene therapy Macromolecule Peptide nucleic acid Photochemical internalization Photodynamic Photosensitizer Protein toxin siRNA... 

Caution During a sininlation, solvent temperature may increase wh ile th e so In te cools. This is particii larly true of sm all solven t molecules, such as water, that can acquire high translational and rotational energies. In contrast, a macromolecule, such as a peptide, retains most of its kinetic energy in vibrational modes. This problem rem ains un solved, an d this n ote of cau tion is provided to advise you to give special care to simulations using solvent. 

To understand the function of a protein at the molecular level, it is important to know its three-dimensional stmcture. The diversity in protein stmcture, as in many other macromolecules, results from the flexibiUty of rotation about single bonds between atoms. Each peptide unit is planar, ie, oJ = 180°, and has two rotational degrees of freedom, specified by the torsion angles ( ) and /, along the polypeptide backbone. The number of torsion angles associated with the side chains, R, varies from residue to residue. The allowed conformations of a protein are those that avoid atomic coUisions between nonbonded atoms. 

Macromolecules are formed from many fragments of smaller molecules which are connected to each other by covalent bonds. For example, protein molecules are assembled from amino acids which are interconnected by peptide bonds (see Fig. 4.1). Typical amino acids are given in Fig. 4.2. 

The field of synthetic enzyme models encompasses attempts to prepare enzymelike functional macromolecules by chemical synthesis [30]. One particularly relevant approach to such enzyme mimics concerns dendrimers, which are treelike synthetic macromolecules with a globular shape similar to a folded protein, and useful in a range of applications including catalysis [31]. Peptide dendrimers, which, like proteins, are composed of amino acids, are particularly well suited as mimics for proteins and enzymes [32]. These dendrimers can be prepared using combinatorial chemistry methods on solid support [33], similar to those used in the context of catalyst and ligand discovery programs in chemistry [34]. Peptide dendrimers used multivalency effects at the dendrimer surface to trigger cooperativity between amino acids, as has been observed in various esterase enzyme models [35]. 

Phase separation microencapsulation procedures are suitable for entrapping water-soluble agents in lactide/glycolide excipients. Generally, the phase separation process involves coacervation of the polymer from an organic solvent by addition of a nonsolvent such as silicone oil. This process has proven useful for microencapsulation of water-soluble peptides and macromolecules (48). 

Rughani RV, Branco MC, Pochan D et al (2010) De novo design of a shear-thin recoverable peptide-based hydrogel capable of intrafibrillar photopolymerization. Macromolecules 43 7924-7930... 

Liu B, Lewis AK, Shen W (2009) Physical hydrogels photo-cross-linked from self- assembled macromers for potential use in tissue engineering. Biomacromolecules 10 3182-3187 Vandermeulen GWM, Tziatzios C, Duncan R et al (2005) Peg-based hybrid block copolymers containing alpha-helical coiled coil peptide sequences control of self- assembly and preliminary biological evaluation. Macromolecules 38 761-769... 

Ozbas B, Kretsinger J, Rajagopal K et al (2004) Salt-triggered peptide folding and consequent self-assembly into hydrogels with tunable modulus. Macromolecules 37 7331-7337... 

Yucel T, Micklitsch CM, Schneider JP et al (2008) Direct observation of early-time hydrogelation in beta-hairpin peptide self-assembly. Macromolecules 41 5763-5772... 

Branco M, Wagner N, Pochan D et al (2009) Release of model macromolecules from selfassembling peptide hydrogels for injectable delivery. Biopolymers 92 318-318... 

Membrane translocating peptides are promising vehicles for the transfer of macromolecules into the tissues. Recent report of Schwarze et al. [249] demonstrated that a signal peptide from Hl-virus could transfer betagalactosidase protein to virtually all tissues in rat after intravenous and intraperitoneal injections. In the case of proteins, folding phenomena affect their membrane translocation and these features may be different for gene-based drugs. 

M. Murakami, Enhanced absorption and lymphatic transport of macromolecules via the rectal route, in Delivery Systems for Peptide Drugs (S. S. Davis, L. Ilium, and E. Tomlinson, eds.), Plenum Press, New York, 1986, p. 177. 

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