Peptide physicochemical

Most of the 2D QSAR methods are based on graph theoretic indices, which have been extensively studied by Randic [29] and Kier and Hall [30,31]. Although these structural indices represent different aspects of molecular structures, their physicochemical meaning is unclear. Successful applications of these topological indices combined with multiple linear regression (MLR) analysis are summarized in Ref. 31. On the other hand, parameters derived from various experiments through chemometric methods have also been used in the study of peptide QSAR, where partial least square (PLS) [32] analysis has been employed [33]. 

Dairy proteins are rich in nutrients and occupy a unique place of importance in food and human nutrition because of their wide acceptance in the world. Milk proteins are important in the diet because of the many health benefits associated with their consumption. The proteins have long been recognized as natural sources of health enhancing bioactive peptides because of their stmctural and physicochemical components as recently reviewed by Livney (2010). 

Henderson, D. E. and Mello, J. A., Physicochemical studies of biologically active peptides by low-temperature reversed-phase high-performance liquid chromatography, /. Chromatogr., 499, 79, 1990. 

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. 

Figure 37 Correlations of log monolayer permeability coefficients for a series of related peptides and various physicochemical indices (see Table 14). In plot (C) the log PC values refer to the immiscible n-heptane/ethylene glycol partitioning system. [Redrawn from Kim et al. (1993) with permission from the publisher.]...

Lutolf MP, Hubbell JA (2003) Synthesis and physicochemical characterization of end-linked poly(ethylene glycol)-co-peptide hydrogels formed by michael-type addition. Biomacromolecules 4 713-722... 

For A/ i 4o and a-synuclein, physicochemical studies documented that the interaction with a membrane was dependent on the presence of acidic lipids and involved a conformational change of the peptide yielding an increase in its a-helical content (Davidson et al., 1998 Hertel et al., 1997 Terzi et al., 1995, 1997). 

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. 

The rates of formation of various cyclic peptides and DKPs have been documented and shown to be affected by a wide range of physicochemical and structural parameters. Goolcharran and Borchardt examined the effects of exogenous (i.e., pH, temperature, buffer species, and concentration) and endogenous (i.e., primary sequences) factors affecting the rate of cyclic dipeptide formation, using the dipeptide analogues of X-Pro-/)-nitroaniline (X-Pro-/>NA where X represents the amino acid residue of the respective cyclic dipeptide). 

A peptide is essentially comprised of L-amino acid residues, and the peptide backbone may be critical to provide physicochemical and functional properties. Diverse functionalities induced by peptides in natural protein hydrolysates are being received with much interest in food industries or alternative-medicinal food sciences. The latest year s researches... 

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. 

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