Peptides physicochemical properties

Rickard, E. C., Strohl, M. M., and Nielsen, R. G., Correlation of electrophoretic mobilities from capillary electrophoresis with physicochemical properties of proteins and peptides, Anal. Biochem., 197, 197, 1991. 

Thus, the optimization of the antimicrobial activity and minimization of cytotoxicity associated with host defense peptides through natural or synthetic means require the balance of a variety of physicochemical properties rather than the optimization of a single attribute. 

Demange P, Wendenbaum S, Linget C, Bateman A, MacLeod J, Dell A, Albrecht AM, Abdallah MA (1989) Pseudomonas Siderophores Structure and Physicochemical Properties of Pyoverdins and Related Peptides. Second Forum on Peptides 174 95... 

Many companies have tried to develop peptidic renin inhibitors. Unfortunately these are rather large molecules and not unexpectedly poor absorption was often observed. The role of physicochemical properties has been discussed for this class of compounds. One of the conclusions was that compounds with higher lipophilicity were better absorbed from the intestine [29]. Absorption and bile elimination rate are both MW-dependent. Lower MW results in better absorption and less bile excretion. The combined influence of molecular size and lipophilicity on absorption of a series of renin inhibitors can be seen from Figure 1.7. The observed iso-size curves are believed to be part of a general sigmoidal relationship between permeability and lipophilicity [30-31] (for further details see Chapter 3). 

Abstract Piperazines and its congeners, (di)keto piperazines are valuable tools in drug discovery, providing a natural path for the process peptide > peptidomimetic > small molecule also called depeptisation. Moreover, they can provide molecular probes to understand molecular pathways for diseases of unmet medical need. However, in order to better understand the design of such value added compounds, the detailed understanding of scope and limitation of their synthesis as well as their 3D structures and associated physicochemical properties is indispensables. Isocyanide multicomponent reaction (MCR) chemistry provides a prime tool for entering the chemical space of (di)(keto)piperazines since not less then 20 different ways exist to access a diversity of related scaffolds. 

A variety of polymeric supports are presently commercially available however, the same resin from different manufacturers has been found to produce markedly different results in terms of yields and purity of the identical peptide under identical experimental conditions/340 In many cases the PEG-PSty resins have proved to be superior compared to PSty resins, a fact which is attributed to the better physicochemical properties of PEG-PSty, e.g. narrow size distribution, high diffusion rate, and excellent swelling with a wide range of solvents. 

Bioactive sequences of up to six amino acid residues known to assume (1- or "/-turns in the bioactive conformation are suitable for such libraries. If the sequence is short, residues have to be added in a manner to retain the desired physicochemical properties of the peptide (e.g., to short polar active sequences hydrophobic residues are preferentially added and vice versa). The choice of the scaffold depends on the number of structure-inducing amino acids such as Gly or Pro present in the native sequence. In absence of such residues scaffolds (1) or (4) (Scheme 24) are selected, whereas if Gly or Pro is present alternative scaffolds can be considered. Then the components of the four stereoisomeric sublibraries of Scheme 26 (or their equivalents if other scaffolds are chosen) are synthesized according to procedures described in the preceding sections. 

The influence of physicochemical properties of liposomes, such as charge density, membrane fluidity, and epitope density, on the immune response elicited by antigens has been extensively studied [37]. In addition to antigens, other immune stimulators that are amphoteric muramyl peptides or lipid-soluble compounds, such as monophosphoryl lipid A or muramyl tripeptidyl-phosphatidylethanolamine, can also be incorporated into liposomes to increase their adjuvant effect in eliciting immune responses [34]. 

Packaging conditions have effects on the stability of protein products. Peptide and protein drugs are high-molecular-weight compounds with unique physicochemical properties. They are extremely sensitive to their microenvironment heat, fight, pH, chemical contaminants, and so on. Trace amounts of metals, plasticizers, and... 

Many reports have indicated the findings that the effects of CyDs on the rectal delivery of drugs depend markedly on vehicle type (hydrophilic or oleaginous), physicochemical properties of the complexes, and an existence of tertiary excipients such as viscous polymers. The enhancing effects of CyDs on the rectal absorption of lipophilic drugs are generally based on the improvement of the release from vehicles and the dissolution rates in rectal fluids, whereas those of CyDs on the rectal delivery of poorly absorbable drugs such as antibiotics, peptides,... 

In the peptide example, twenty measures of physicochemical properties of amino acids were compiled (Table 6.4). Plots of the first three PCs of these data are given in Table 6.14. The use of the PC I-scores in the design of QSAR experiments are illustrated by the peptide example in the Experimental design section. 

Figure 6.14. Scatter plot of t-scores of (a) PC, versus PC2 and (b) PC, versus PC3 calculated from the physicochemical properties of amino acids in the peptide example.

The peptide example illustrates these points. The PC r-scores of the first three principal components of the physicochemical properties of amino acids are plotted in Figure 6.14. This space is well spanned by arg, asp, gly, ile and trp (Figure 6.24), which may therefore form a basis for construction of a fractional factorial design of a QSAR as previously suggested [6]. 

---