Peptides heterogeneity

Wang, X., A.L. DeVries, C.-H. C. Cheng (1995). Genomic basis for antifreeze peptide heterogeneity and abundance in an Antarctic eel pout Gene structures and organization. Mol. Mar. Biol. Biotech. 4 135-147. 

If peptide residues are converted to peptoid residues, the conformational heterogeneity of the polymer backbone is likely to increase due to cis/trans isomerization at amide bonds. This will lead to an enhanced loss of conformational entropy upon peptoid/protein association, which could adversely affect binding thermodynamics. A potential solution is the judicious placement of bulky peptoid side chains that constrain backbone dihedral angles. 

The coupling of solute transport in the GI lumen with solute lumenal metabolism (homogeneous reaction) and membrane metabolism (heterogeneous reaction) has been discussed by Sinko et al. [54] and is more generally treated in Cussler s text [55], At the cellular level, solute metabolism can occur at the mucosal membrane, in the enterocyte cytosol, and in the endoplasmic reticulum (or microsomal compartment). For peptide drugs, the extent of hydrolysis by lumenal and membrane-bound peptidases reduces drug availability for intestinal absorption [56], Preferential hydrolysis (metabolic specificity) has been targeted for reconversion... 

One of the cornerstones of combinatorial synthesis has been the development of solid-phase organic synthesis (SPOS) based on the original Merrifield method for peptide preparation [19]. Because transformations on insoluble polymer supports should enable chemical reactions to be driven to completion and enable simple product purification by filtration, combinatorial chemistry has been primarily performed by SPOS [19-23], Nonetheless, solid-phase synthesis has several shortcomings, because of the nature of heterogeneous reaction conditions. Nonlinear kinetic behavior, slow reaction, solvation problems, and degradation of the polymer support, because of the long reactions, are some of the problems typically experienced in SPOS. It is, therefore, not surprising that the first applications of microwave-assisted solid-phase synthesis were reported as early 1992 [24],... 

Unlike other Eukarya, animal cells lack cell walls, though they tend to be surrounded by a highly developed glycocalyx of up to 140 nm in thickness [108]. This diffuse layer of densely packed oligosaccharides has a heterogeneous composition and is connected to the membrane via lipids or integral proteins. The boundary of the cell usually extends beyond the mere lipid bilayer with its embedded proteins, and the extracellular structures provide initial sites of interaction or are themselves targets for MAPs such as antimicrobial peptides [115]. 

Yallampalli, C., Chauhan, M., Thota, C.S., Kondapaka, S., and Wimalawansa, SJ. 2002. Calcitonin gene-related peptide in pregnancy and its emerging receptor heterogeneity. Trends in Endocrinology and Metabolism 13(6), 263-269. 

In order to influence mast-cell function, peptides must be made available at sites very near to tissue mast cells. One means of accomplishing this is by specific peptidergic innervation. This would not necessarily require a classical synaptic morphology, but only the termination of nerves within the vicinity of mast cells [1,3]. Modulation of mast-cell secretion by peptides of neural origin is particularly attractive, for it would allow for a restricted, localized expression of peptide action in specific target tissues because of the selective distribution of each peptide within particular neurones. Moreover, this could be further modified and restricted by differing mast cell specificities. (Heterogeneity of mast cell responsiveness to peptide stimulation has been well documented [52, 53 ].) The result would permit a well-localized tissue response without systemic manifestation [3]. 

SP seems to be the only peptide capable of stimulating histamine release from mucosal mast cells [52] and generally exhibits a pronounced heterogeneity among various tissues and between species [106],... 

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