Proteomics - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 403

A second issue is that permeation enhancers may potentiate the carcinogenicity of
such compounds if included in formulation components. The third major issue is
their erratic and abrupt systemic absorption, leading to toxicity. Hence, it is critical
to develop highly efficacious, biocompatible, biodegradable, user-friendly, and non-
toxic absorption promoters.
8.5 Physical Biochemistry of Proteins and Peptides
Proteins and peptides have attracted a great deal of attention among scientists in
terms of their potential use in diagnostics, therapeutics, and drug delivery systems.
For this, scientists must be familiar with the special structures of peptides, the physi-
cal and chemical properties of peptides, and so forth. Chemically, proteins and pep-
tides, both are made up of amino acids only with nominal difference of peptides
containing lesser than 100 amino acid residues in their structure.
8.5.1 Peptide and Protein Structure
Peptide chains are the key components of all the proteins. A peptide chain of a mam-
malian peptide or protein consists of a polyamide backbone made up of carbon atoms
interspersed between amide groups and alkyl side chains. The peptide chain is formed
by condensation of amino acids that involves formation of peptide bonds between the
carboxylic acid C terminal and the amino group. In the C-terminus, one end is carboxylic
acid while the other end is a free amino group that is known as the N-terminus. The car-
bon atoms present at the backbone are asymmetric and have an L-absolute configuration.
The presence of these chiral centers is responsible for the conformational arrangement of
proteins and thereby their stability. There are in all 22 amino acids in the body of a mam-
mal. The side chains are either reactive or inert, depending upon the presence and type
of amino acids. The presence of amino acids like arginine, aspartic acid, glutamic acid,
and so on, renders the protein molecules quite reactive while those with alanine, gly-
cine, leucine, and so forth, are very inert. These alkyl side chains are also responsible for
hydrophilicity or hydrpophobicity of the protein molecule and for the formation of conju-
gated proteins. These side chains get covalently linked to sugar, phosphate, lipids, nucleic
acids, and so on. These covalent linkages with diverse biomolecules impart the chemical
and physical properties that render them biologically active and chemically stable. Amino
acids are the building blocks of peptides and proteins; the latter are amphoteric in nature.
One of the important physiochemical properties possessed by proteins is their isoelectric
point, or pH. The isoelectric point, or pH, is defined as the pH of an aqueous solution at
which there is no net charge on the molecule, in other words, the molecule is electrically
neutral and does not migrate in an electric field on applying external potential. At this pH,
due to the absence of either type of charge, the protein or peptide tends to precipitate out
from the aqueous solution.
Peptide chain conformation is deduced by the amino acid sequences held together
by means of disulfide linkages and total conformational energy. Conformational
energy is the sum total of all energies of interactions. These energies of interactions